Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:26:57 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2797
Identification
Common NameImipramine
ClassSmall Molecule
DescriptionImipramine, the prototypical tricyclic antidepressant (TCA), is a dibenzazepine-derivative TCA. TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, imipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as imipramine and amitriptyline, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. Imipramine has less sedative and anticholinergic effects than the tertiary amine TCAs, amitriptyline and clomipramine. See toxicity section below for a complete listing of side effects. Imipramine may be used to treat depression and nocturnal enuresis in children. Unlabeled indications include chronic and neuropathic pain (including diabetic neuropathy), panic disorder, attention-deficit/hyperactivity disorder (ADHD), and post-traumatic stress disorder (PTSD).
Compound Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressive Agent, Tricyclic
  • Drug
  • Food Toxin
  • Metabolite
  • Norepinephrine Reuptake Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
10,11-dihydro-N,N-Dimethyl-5H-dibenz[b,F]azepine-5-propanamine
3-(5H-DIBENZO[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine
5-[3-(dimethylamino)Propyl]-10,11-dihydro-5H-dibenz[b,F]azepine
Antidep
Antideprin
Berkomine
Chimoreptin
Declomipramine
Depsonil
Depsonil-PM
Dimipressin
DPID
Dyna-Zina
Dynaprin
Elamin
Eupramin
Feinalmin
Fronil
Imavate
Imidobenzyle
Imidol
Imilanyle
Imipramin
Imipramin Dak
Imipraminum
Imiprex
Imizine
Irmin
Janimine
Lofepramine
Melipramin
Melipramine
N-(gamma-Dimethylaminopropyl)iminodibenzyl
N-(γ-dimethylaminopropyl)iminodibenzyl
Pramin
Psychoforin
Surmontil
Surplix
Teperine
Timolet
Tofranil
Tofranil base
Tofranil-Pm
Trimipramine Maleate
Chemical FormulaC19H24N2
Average Molecular Mass280.407 g/mol
Monoisotopic Mass280.194 g/mol
CAS Registry Number50-49-7
IUPAC Name(3-{2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)dimethylamine
Traditional Name(3-{2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)dimethylamine
SMILESCN(C)CCCN1C2=CC=CC=C2CCC2=CC=CC=C12
InChI IdentifierInChI=1S/C19H24N2/c1-20(2)14-7-15-21-18-10-5-3-8-16(18)12-13-17-9-4-6-11-19(17)21/h3-6,8-11H,7,12-15H2,1-2H3
InChI KeyInChIKey=BCGWQEUPMDMJNV-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzazepines. Dibenzazepines are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzazepines
Sub ClassDibenzazepines
Direct ParentDibenzazepines
Alternative Parents
Substituents
  • Dibenzazepine
  • Alkyldiarylamine
  • Tertiary aliphatic/aromatic amine
  • Azepine
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point174-175°C
Boiling Point160°C at 1.00E-01 mm Hg
Solubility18.2 mg/L (at 24°C)
LogP4.8
Predicted Properties
PropertyValueSource
Water Solubility0.066 g/LALOGPS
logP4.53ALOGPS
logP4.28ChemAxon
logS-3.6ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity90.61 m³·mol⁻¹ChemAxon
Polarizability33.39 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0019-7490000000-3fb4d40b6a219f088ec8View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0019-7490000000-3fb4d40b6a219f088ec8View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-7490000000-746fcd08b0a7d6e7bc83View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-9000000000-55d924fd00e5b357ce9eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-9000000000-eb3c0ecdffc5d9d95e33View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0ab9-9432000000-033c51459b692622ee7dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (Unknown) , Positivesplash10-0019-7490000000-bb99ef31a755d9f6ba14View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-052r-9010000000-961429188e57c1480db8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-1090000000-d8b2753be1e55651ebe7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0019-5190000000-884d5f80618ae379a408View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000f-9420000000-655018838b0eb1b10c77View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0090000000-115aa4768e53e232aa16View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004l-1590000000-bf5870eaefcecc8340c7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-2910000000-568ea79e9375b6365408View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0543-8890000000-6cf8e84f007ce7c750f2View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureRapidly and well absorbed after oral administration. Bioavailability is approximately 43%. Peak plasma concentrations usually attained 1 - 2 hours following oral administration. Absorption is unaffected by food.
Mechanism of ToxicityImipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, which is thought to contribute to relieving symptoms of depression. In addition to acutely inhibiting neurotransmitter re-uptake, imipramine causes down-regulation of cerebral cortical beta-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission.
MetabolismExclusively metabolized by the liver. Imipramine is converted in the liver by various CYP isoenzymes (e.g. CYP1A2, CYP2D6, CYP3A4, CYP2C9) to active metabolites desipramine and 2-hydroxydesipramine. Route of Elimination: Approximately 40% of an orally administered dose is eliminated in urine within 24 hours, 70% in 72 hours. Small amounts are eliminated in feces via the biliary elimination. Half Life: Imipramine - 8-20 hours; Desipramine (active metabolite) - up to 125 hours
Toxicity ValuesLD50: 355 to 682 mg/kg (oral, rat).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older. May also be used to manage panic disorders, with or without agoraphobia, as a second line agent in ADHD, management of eating disorders, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, and for symptomatic treatment of postherpetic neuralgia.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsAntagonism of the histamine H1 and α1 receptors can lead to sedation and hypotension. Antimuscarinic and anticholinergic side effects such as blurred vision, dry mouth, constipation and urine retention may occur. Cardiotoxicity may occur with high doses of imipramine. Cardiovascular side effects in postural hypotension, tachycardia, hypertension, ECG changes and congestive heart failure. Psychotoxic effects include impaired memory and delirium. Induction of hypomanic or manic episodes may occur in patients with a history of bipolar disorder. Withdrawal symptoms include GI disturbances (e.g. nausea, vomiting, abdominal pain, diarrhea), anxiety, insomnia, nervousness, headache and malaise.
TreatmentObtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at anytime during this period, extended monitoring is required. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00458
HMDB IDHMDB01848
PubChem Compound ID3696
ChEMBL IDCHEMBL11
ChemSpider ID3568
KEGG IDC07049
UniProt IDNot Available
OMIM ID
ChEBI ID5881
BioCyc IDNot Available
CTD IDNot Available
Stitch IDImipramine
PDB IDIXX
ACToR IDNot Available
Wikipedia LinkImipramine
References
Synthesis Reference

U.S. Patent 2,554,736.

MSDSLink
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00015 uMNot AvailableBindingDB 50010859
Inhibitory0.00077 uMNot AvailableBindingDB 50010859
Inhibitory0.0013 uMNot AvailableBindingDB 50010859
Inhibitory0.0014 uMNot AvailableBindingDB 50010859
Inhibitory0.005 uMNot AvailableBindingDB 50010859
Inhibitory0.00757 uMNot AvailableBindingDB 50010859
Inhibitory0.019 uMNot AvailableBindingDB 50010859
Inhibitory0.02 uMNot AvailableBindingDB 50010859
IC500.0073 uMNot AvailableBindingDB 50010859
IC500.008 uMNot AvailableBindingDB 50010859
IC500.029 uMNot AvailableBindingDB 50010859
References
  1. Leboyer M, Quintin P, Manivet P, Varoquaux O, Allilaire JF, Launay JM: Decreased serotonin transporter binding in unaffected relatives of manic depressive patients. Biol Psychiatry. 1999 Dec 15;46(12):1703-6. [10624553 ]
  2. Scholze P, Zwach J, Kattinger A, Pifl C, Singer EA, Sitte HH: Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter. J Pharmacol Exp Ther. 2000 Jun;293(3):870-8. [10869387 ]
  3. Quintin P, Benkelfat C, Launay JM, Arnulf I, Pointereau-Bellenger A, Barbault S, Alvarez JC, Varoquaux O, Perez-Diaz F, Jouvent R, Leboyer M: Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder. Biol Psychiatry. 2001 Aug 1;50(3):184-90. [11513817 ]
  4. Goulet M, Miller GM, Bendor J, Liu S, Meltzer PC, Madras BK: Non-amines, drugs without an amine nitrogen, potently block serotonin transport: novel antidepressant candidates? Synapse. 2001 Dec 1;42(3):129-40. [11746710 ]
  5. Barkan T, Gurwitz D, Levy G, Weizman A, Rehavi M: Biochemical and pharmacological characterization of the serotonin transporter in human peripheral blood lymphocytes. Eur Neuropsychopharmacol. 2004 May;14(3):237-43. [15056483 ]
  6. Hayashi S, Nakata E, Morita A, Mizuno K, Yamamura K, Kato A, Ohashi K: Discovery of {1-[4-(2-{hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl}-1H-benzimidazol-1-yl)piperidin- 1-yl]cyclooctyl}methanol, systemically potent novel non-peptide agonist of nociceptin/orphanin FQ receptor as analgesic for the treatment of neuropathic pain: design, synthesis, and structure-activity relationships. Bioorg Med Chem. 2010 Nov 1;18(21):7675-99. doi: 10.1016/j.bmc.2010.07.034. Epub 2010 Jul 21. [20875743 ]
  7. Kelly JX, Smilkstein MJ, Cooper RA, Lane KD, Johnson RA, Janowsky A, Dodean RA, Hinrichs DJ, Winter R, Riscoe M: Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. Antimicrob Agents Chemother. 2007 Nov;51(11):4133-40. Epub 2007 Sep 10. [17846138 ]
  8. Bright SA, Brinko A, Larsen MT, Sinning S, Williams DC, Jensen HH: Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1220-4. doi: 10.1016/j.bmcl.2013.01.020. Epub 2013 Jan 12. [23385211 ]
  9. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE: Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl). 1996 Mar;124(1-2):57-73. [8935801 ]
  10. Dolusic E, Larrieu P, Moineaux L, Stroobant V, Pilotte L, Colau D, Pochet L, Van den Eynde B, Masereel B, Wouters J, Frederick R: Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators. J Med Chem. 2011 Aug 11;54(15):5320-34. doi: 10.1021/jm2006782. Epub 2011 Jul 18. [21726069 ]
  11. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB: Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther. 1997 Dec;283(3):1305-22. [9400006 ]
  12. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
  13. Peddi S, Roth BL, Glennon RA, Westkaemper RB: Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA). Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. [15081025 ]
  14. White JD, Juniku R, Huang K, Yang J, Wong DT: Synthesis of 1,1-[1-naphthyloxy-2-thiophenyl]-2-methylaminomethylcyclopropanes and their evaluation as inhibitors of serotonin, norepinephrine, and dopamine transporters. J Med Chem. 2009 Oct 8;52(19):5872-9. doi: 10.1021/jm900847b. [19791802 ]
  15. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW: Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711. [12431845 ]
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.016 uMNot AvailableBindingDB 50010859
Inhibitory0.02 uMNot AvailableBindingDB 50010859
Inhibitory0.037 uMNot AvailableBindingDB 50010859
Inhibitory0.098 uMNot AvailableBindingDB 50010859
Inhibitory0.118 uMNot AvailableBindingDB 50010859
Inhibitory0.142 uMNot AvailableBindingDB 50010859
IC500.074 uMNot AvailableBindingDB 50010859
References
  1. Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. [16893531 ]
  2. Dziedzicka-Wasylewska M, Faron-Gorecka A, Kusmider M, Drozdowska E, Rogoz Z, Siwanowicz J, Caron MG, Bonisch H: Effect of antidepressant drugs in mice lacking the norepinephrine transporter. Neuropsychopharmacology. 2006 Nov;31(11):2424-32. Epub 2006 Mar 22. [16554743 ]
  3. Anton M, Wagner B, Haubner R, Bodenstein C, Essien BE, Bonisch H, Schwaiger M, Gansbacher B, Weber WA: Use of the norepinephrine transporter as a reporter gene for non-invasive imaging of genetically modified cells. J Gene Med. 2004 Jan;6(1):119-26. [14716684 ]
  4. Kantor L, Hewlett GH, Park YH, Richardson-Burns SM, Mellon MJ, Gnegy ME: Protein kinase C and intracellular calcium are required for amphetamine-mediated dopamine release via the norepinephrine transporter in undifferentiated PC12 cells. J Pharmacol Exp Ther. 2001 Jun;297(3):1016-24. [11356924 ]
  5. Tatsumi M, Jansen K, Blakely RD, Richelson E: Pharmacological profile of neuroleptics at human monoamine transporters. Eur J Pharmacol. 1999 Mar 5;368(2-3):277-83. [10193665 ]
  6. Kelly JX, Smilkstein MJ, Cooper RA, Lane KD, Johnson RA, Janowsky A, Dodean RA, Hinrichs DJ, Winter R, Riscoe M: Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. Antimicrob Agents Chemother. 2007 Nov;51(11):4133-40. Epub 2007 Sep 10. [17846138 ]
  7. Peddi S, Roth BL, Glennon RA, Westkaemper RB: Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA). Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. [15081025 ]
  8. Owens MJ, Morgan WN, Plott SJ, Nemeroff CB: Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther. 1997 Dec;283(3):1305-22. [9400006 ]
  9. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
  10. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW: Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711. [12431845 ]
  11. Paczkowski FA, Bryan-Lluka LJ, Porzgen P, Bruss M, Bonisch H: Comparison of the pharmacological properties of cloned rat, human, and bovine norepinephrine transporters. J Pharmacol Exp Ther. 1999 Aug;290(2):761-7. [10411589 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC503.388 uMNot AvailableBindingDB 50010859
IC503.38844 uMNot AvailableBindingDB 50010859
IC503.4 uMNot AvailableBindingDB 50010859
References
  1. Teschemacher AG, Seward EP, Hancox JC, Witchel HJ: Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. Br J Pharmacol. 1999 Sep;128(2):479-85. [10510461 ]
  2. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
  3. Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
  4. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
  5. Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
  6. Ermondi G, Visentin S, Caron G: GRIND-based 3D-QSAR and CoMFA to investigate topics dominated by hydrophobic interactions: the case of hERG K+ channel blockers. Eur J Med Chem. 2009 May;44(5):1926-32. doi: 10.1016/j.ejmech.2008.11.009. Epub 2008 Nov 28. [19110341 ]
  7. Cavalli A, Poluzzi E, De Ponti F, Recanatini M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J Med Chem. 2002 Aug 29;45(18):3844-53. [12190308 ]
  8. Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [15272206 ]
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.094 uMNot AvailableBindingDB 50010859
Inhibitory0.16 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Zanoveli JM, Nogueira RL, Zangrossi H Jr: Chronic imipramine treatment sensitizes 5-HT1A and 5-HT 2 A receptors in the dorsal periaqueductal gray matter: evidence from the elevated T-maze test of anxiety. Behav Pharmacol. 2005 Nov;16(7):543-52. [16170231 ]
  3. Peddi S, Roth BL, Glennon RA, Westkaemper RB: Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA). Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. [15081025 ]
  4. Runyon SP, Savage JE, Taroua M, Roth BL, Glennon RA, Westkaemper RB: Influence of chain length and N-alkylation on the selective serotonin receptor ligand 9-(aminomethyl)-9,10-dihydroanthracene. Bioorg Med Chem Lett. 2001 Mar 12;11(5):655-8. [11266163 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.15 uMNot AvailableBindingDB 50010859
Inhibitory0.16 uMNot AvailableBindingDB 50010859
References
  1. Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J: Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996 Aug;126(3):234-40. [8876023 ]
  2. Roth BL: Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry. 1994 Jun;6(2):67-78. [7804391 ]
  3. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  4. Peddi S, Roth BL, Glennon RA, Westkaemper RB: Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA). Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. [15081025 ]
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory8.5 uMNot AvailableBindingDB 50010859
Inhibitory>10 uMNot AvailableBindingDB 50010859
IC5025.6 uMNot AvailableBindingDB 50010859
References
  1. Melikian HE, Buckley KM: Membrane trafficking regulates the activity of the human dopamine transporter. J Neurosci. 1999 Sep 15;19(18):7699-710. [10479674 ]
  2. Kelly JX, Smilkstein MJ, Cooper RA, Lane KD, Johnson RA, Janowsky A, Dodean RA, Hinrichs DJ, Winter R, Riscoe M: Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. Antimicrob Agents Chemother. 2007 Nov;51(11):4133-40. Epub 2007 Sep 10. [17846138 ]
  3. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [9537821 ]
  4. Bymaster FP, Katner JS, Nelson DL, Hemrick-Luecke SK, Threlkeld PG, Heiligenstein JH, Morin SM, Gehlert DR, Perry KW: Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacology. 2002 Nov;27(5):699-711. [12431845 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory5.8 uMNot AvailableBindingDB 50010859
Inhibitory>10 uMNot AvailableBindingDB 50010859
References
  1. Haddjeri N, Blier P, de Montigny C: Long-term antidepressant treatments result in a tonic activation of forebrain 5-HT1A receptors. J Neurosci. 1998 Dec 1;18(23):10150-6. [9822768 ]
  2. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  3. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00013 uMNot AvailableBindingDB 50010859
Inhibitory0.046 uMNot AvailableBindingDB 50010859
Inhibitory0.088 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Kovacs I, Yamamura HI, Waite SL, Varga EV, Roeske WR: Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line. J Pharmacol Exp Ther. 1998 Feb;284(2):500-7. [9454790 ]
  3. Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
References
  1. Grimaldi B, Bonnin A, Fillion MP, Ruat M, Traiffort E, Fillion G: Characterization of 5-ht6 receptor and expression of 5-ht6 mRNA in the rat brain during ontogenetic development. Naunyn Schmiedebergs Arch Pharmacol. 1998 Apr;357(4):393-400. [9606024 ]
  2. Roth BL: Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry. 1994 Jun;6(2):67-78. [7804391 ]
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
Molecular Weight:
53554.43 Da
References
  1. Lucchelli A, Santagostino-Barbone MG, D'Agostino G, Masoero E, Tonini M: The interaction of antidepressant drugs with enteric 5-HT7 receptors. Naunyn Schmiedebergs Arch Pharmacol. 2000 Sep;362(3):284-9. [10997731 ]
  2. Roth BL: Multiple serotonin receptors: clinical and experimental aspects. Ann Clin Psychiatry. 1994 Jun;6(2):67-78. [7804391 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [20363235 ]
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.016 uMNot AvailableBindingDB 50010859
Inhibitory0.037 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.042 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.06 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.112 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
  2. Stanton T, Bolden-Watson C, Cusack B, Richelson E: Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics. Biochem Pharmacol. 1993 Jun 9;45(11):2352-4. [8100134 ]
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5017.1 uMNot AvailableBindingDB 50010859
IC5037 uMNot AvailableBindingDB 50010859
References
  1. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [18788725 ]
  2. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
General Function:
Purine nucleoside binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
ADORA1
Uniprot ID:
P30542
Molecular Weight:
36511.325 Da
References
  1. Zahorodna A, Bijak M, Hess G: Differential effects of repeated imipramine on hippocampal responsiveness to adenosine and serotonin. Eur Neuropsychopharmacol. 2002 Aug;12(4):355-60. [12126876 ]
General Function:
G-protein coupled adenosine receptor activity
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. Possible role in reproduction.
Gene Name:
ADORA3
Uniprot ID:
P0DMS8
Molecular Weight:
36184.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.0044 uMNot AvailableBindingDB 50010859
References
  1. Minetti P, Tinti MO, Carminati P, Castorina M, Di Cesare MA, Di Serio S, Gallo G, Ghirardi O, Giorgi F, Giorgi L, Piersanti G, Bartoccini F, Tarzia G: 2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization. J Med Chem. 2005 Nov 3;48(22):6887-96. [16250647 ]
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM2
Uniprot ID:
P19652
Molecular Weight:
23602.43 Da
References
  1. Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [8946472 ]
General Function:
Protein heterodimerization activity
Specific Function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [20363235 ]
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [20363235 ]
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory3.1 uMNot AvailableBindingDB 50010859
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
23. D(1) dopamine receptor (Protein Group)
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Included Proteins:
P21728 , P21918
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50010859
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.726 uMNot AvailableBindingDB 50010859
References
  1. Peddi S, Roth BL, Glennon RA, Westkaemper RB: Structural determinants for high 5-HT(2A) receptor affinity of spiro[9,10-dihydroanthracene]-9,3(')-pyrrolidine (SpAMDA). Bioorg Med Chem Lett. 2004 May 3;14(9):2279-83. [15081025 ]
General Function:
Not Available
Specific Function:
Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
Gene Name:
FBF1
Uniprot ID:
Q8TES7
Molecular Weight:
125445.19 Da
References
  1. Yoo MJ, Hage DS: Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16. [20956006 ]
General Function:
Histamine receptor activity
Specific Function:
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity).
Gene Name:
HRH2
Uniprot ID:
P25021
Molecular Weight:
40097.65 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.9 uMNot AvailableBindingDB 50010859
References
  1. Quinones-Torrelo C, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ: Development of predictive retention-activity relationship models of tricyclic antidepressants by micellar liquid chromatography. J Med Chem. 1999 Aug 12;42(16):3154-62. [10447960 ]
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5010 uMNot AvailableBindingDB 50010859
References
  1. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
General Function:
Drug transmembrane transporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A2
Uniprot ID:
Q86VL8
Molecular Weight:
65083.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50010859
References
  1. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60073.205 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [7855217 ]
General Function:
Voltage-gated potassium channel activity
Specific Function:
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhytm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).
Gene Name:
KCND2
Uniprot ID:
Q9NZV8
Molecular Weight:
70535.825 Da
References
  1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [9781919 ]
General Function:
Metal ion binding
Specific Function:
Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
Gene Name:
KCND3
Uniprot ID:
Q9UK17
Molecular Weight:
73450.53 Da
References
  1. Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [9781919 ]
General Function:
Phosphorelay sensor kinase activity
Specific Function:
Pore-forming (alpha) subunit of a voltage-gated delayed rectifier potassium channel (PubMed:22732247). Channel properties may be modulated by subunit assembly, but not by cyclic nucleotides (By similarity). Mediates IK(NI) current in myoblasts (PubMed:9738473). Involved in the regulation of cell proliferation and differentiation, in particular adipogenic and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (MSCs) (PubMed:23881642).
Gene Name:
KCNH1
Uniprot ID:
O95259
Molecular Weight:
111421.76 Da
References
  1. Roy J, Vantol B, Cowley EA, Blay J, Linsdell P: Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7. Oncol Rep. 2008 Jun;19(6):1511-6. [18497958 ]
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.6 uMNot AvailableBindingDB 50010859
References
  1. Kido Y, Matsson P, Giacomini KM: Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. J Med Chem. 2011 Jul 14;54(13):4548-58. doi: 10.1021/jm2001629. Epub 2011 Jun 8. [21599003 ]