Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:28:27 UTC
Update Date2014-12-24 20:25:55 UTC
Accession NumberT3D2996
Identification
Common NameDesipramine
ClassSmall Molecule
DescriptionDesipramine hydrochloride is a dibenzazepine-derivative tricyclic antidepressant (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, desipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, desipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Secondary amine TCAs, such as desipramine and nortriptyline, are more potent inhibitors of norepinephrine reuptake than tertiary amine TCAs, such as amitriptyline and doxepine. 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. See toxicity section below for a complete listing of side effects. Desipramine exerts less anticholinergic and sedative side effects compared to tertiary amine TCAs, such as amitriptyline and clomipramine. Desipramine may be used to treat depression, neuropathic pain (unlabeled use), agitation and insomnia (unlabeled use) and attention-deficit hyperactivity disorder (unlabeled use).
Compound Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressant
  • Antidepressive Agent
  • Antidepressive Agent, Tricyclic
  • Drug
  • Enzyme Inhibitor
  • Metabolite
  • Norepinephrine Reuptake Inhibitor
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3-(10,11-DIHYDRO-5H-dibenzo[b,F]azepin-5-yl)-N-methylpropan-1-amine
5-(gamma-Methylaminopropyl)iminodibenzyl
5-(γ-methylaminopropyl)iminodibenzyl
Demethylimipramine
Desimipramine
Desimpramine
Desipramin
Desipramina
Desipraminum
Desmethylimipramine
Dezipramine
Dimethylimipramine
DMI
Methylaminopropyliminodibenzyl
Monodemethylimipramine
N-(3-methylaminopropyl)iminobibenzyl
Norimipramine
Norpramin
Norpramine
Pertofran
Pertofrane
Chemical FormulaC18H22N2
Average Molecular Mass266.381 g/mol
Monoisotopic Mass266.178 g/mol
CAS Registry Number50-47-5
IUPAC Name(3-{2-azatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-yl}propyl)(methyl)amine
Traditional Namedesipramine
SMILESCNCCCN1C2=CC=CC=C2CCC2=CC=CC=C12
InChI IdentifierInChI=1S/C18H22N2/c1-19-13-6-14-20-17-9-4-2-7-15(17)11-12-16-8-3-5-10-18(16)20/h2-5,7-10,19H,6,11-14H2,1H3
InChI KeyInChIKey=HCYAFALTSJYZDH-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 amine
  • Azacycle
  • Secondary amine
  • Secondary aliphatic amine
  • 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
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point214-218°C
Boiling PointNot Available
Solubility58.6 mg/L (at 24°C)
LogP4.9
Predicted Properties
PropertyValueSource
Water Solubility0.04 g/LALOGPS
logP4.02ALOGPS
logP3.9ChemAxon
logS-3.8ALOGPS
pKa (Strongest Basic)10.02ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area15.27 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity85.31 m³·mol⁻¹ChemAxon
Polarizability31.74 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)splash10-0544-7980000000-e155fe1ae5cd0aa22da3View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0544-7980000000-e155fe1ae5cd0aa22da3View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4l-7290000000-31dae7fdcf8b3c932db1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014r-0090000000-80dacb090470e582c8f8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00rl-5190000000-a15a250e113df7cffdc6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9520000000-8eb58abd95c114e6b333View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0090000000-c941aca18da7b3ecea74View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014l-1590000000-66b8b8550a46a769b52cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-2900000000-eac7951bde437dcb062dView in MoNA
MSMass Spectrum (Electron Ionization)splash10-0006-4970000000-810535cb33c37107abc5View in MoNA
Toxicity Profile
Route of ExposureDesipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. It undergoes extensive first-pass metabolism. Peak plasma concentrations are attained 4 - 6 hours following oral administration.
Mechanism of ToxicityDesipramine is a tricyclic antidepressant (TCA) that selectively blocks reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases stimulation of the post-synaptic neuron. Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system.
MetabolismDesipramine is extensively metabolized in the liver by CYP2D6 (major) and CYP1A2 (minor) to 2-hydroxydesipramine, an active metabolite. 2-hydroxydesipramine is thought to retain some amine reuptake inhibition and may possess cardiac depressant activity. The 2-hydroxylation metabolic pathway of desipramine is under genetic control. Route of Elimination: Desipramine is metabolized in the liver, and approximately 70% is excreted in the urine. Half Life: 7-60+ hours; 70% eliminated renally
Toxicity ValuesLD50: 290 mg/kg (Mouse) (1) LD50: 320 mg/kg (Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
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 any time during this period, extended monitoring is required. Follow ECG, renal function, CPK, and arterial blood gasses as clinically indicated. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01151
HMDB IDHMDB15282
PubChem Compound ID2995
ChEMBL IDCHEMBL72
ChemSpider ID2888
KEGG IDC06943
UniProt IDNot Available
OMIM ID
ChEBI ID47781
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDesipramine
PDB IDDSM
ACToR IDNot Available
Wikipedia LinkDesipramine
References
Synthesis Reference

Biel, J.H.and Judd, C.I.; US. Patent 3,454,554; July 8,1969; assigned to Colgate Palmolive Co.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Drugs.com [Link]
  3. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
Inhibitory0.0006 uMNot AvailableBindingDB 35229
Inhibitory0.00063 uMNot AvailableBindingDB 35229
Inhibitory0.00083 uMNot AvailableBindingDB 35229
Inhibitory0.001 uMNot AvailableBindingDB 50010869
Inhibitory0.0021 uMNot AvailableBindingDB 35229
Inhibitory0.0034 uMNot AvailableBindingDB 50010869
Inhibitory0.0035 uMNot AvailableBindingDB 35229
Inhibitory0.0038 uMNot AvailableBindingDB 35229
Inhibitory0.0039 uMNot AvailableBindingDB 35229
Inhibitory0.0041 uMNot AvailableBindingDB 35229
Inhibitory0.00511 uMNot AvailableBindingDB 50010869
Inhibitory0.00854 uMNot AvailableBindingDB 35229
IC500.00093 uMNot AvailableBindingDB 50010869
IC500.0033 uMNot AvailableBindingDB 50010869
IC500.0034 uMNot AvailableBindingDB 50010869
IC500.0039 uMNot AvailableBindingDB 50010869
IC500.0042 uMNot AvailableBindingDB 50010869
Dissociation0.00083 uMNot AvailableBindingDB 50010869
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Zavosh A, Schaefer J, Ferrel A, Figlewicz DP: Desipramine treatment decreases 3H-nisoxetine binding and norepinephrine transporter mRNA in SK-N-SHSY5Y cells. Brain Res Bull. 1999 Jul 1;49(4):291-5. [10424850 ]
  3. Weinshenker D, White SS, Javors MA, Palmiter RD, Szot P: Regulation of norepinephrine transporter abundance by catecholamines and desipramine in vivo. Brain Res. 2002 Aug 16;946(2):239-46. [12137927 ]
  4. Bryan-Lluka LJ, Bonisch H, Lewis RJ: chi-Conopeptide MrIA partially overlaps desipramine and cocaine binding sites on the human norepinephrine transporter. J Biol Chem. 2003 Oct 10;278(41):40324-9. Epub 2003 Jul 1. [12837768 ]
  5. Zhu MY, Kyle PB, Hume AS, Ordway GA: The persistent membrane retention of desipramine causes lasting inhibition of norepinephrine transporter function. Neurochem Res. 2004 Feb;29(2):419-27. [15002740 ]
  6. Ordway GA, Jia W, Li J, Zhu MY, Mandela P, Pan J: Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation. J Neurosci Methods. 2005 Apr 30;143(2):217-25. Epub 2004 Dec 30. [15814154 ]
  7. Altenbach RJ, Black LA, Strakhova MI, Manelli AM, Carr TL, Marsh KC, Wetter JM, Wensink EJ, Hsieh GC, Honore P, Garrison TR, Brioni JD, Cowart MD: Diaryldiamines with dual inhibition of the histamine H(3) receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain. J Med Chem. 2010 Nov 11;53(21):7869-73. doi: 10.1021/jm100666w. [20945906 ]
  8. Cheng MC, Li CY, Ko HC, Ko FN, Lin YL, Wu TS: Antidepressant principles of the roots of Polygala tenuifolia. J Nat Prod. 2006 Sep;69(9):1305-9. [16989524 ]
  9. Vu AT, Cohn ST, Zhang P, Kim CY, Mahaney PE, Bray JA, Johnston GH, Koury EJ, Cosmi SA, Deecher DC, Smith VA, Harrison JE, Leventhal L, Whiteside GT, Kennedy JD, Trybulski EJ: 1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective norepinephrine reuptake inhibitors. J Med Chem. 2010 Mar 11;53(5):2051-62. doi: 10.1021/jm901559e. [20131864 ]
  10. Mahaney PE, Gavrin LK, Trybulski EJ, Stack GP, Vu TA, Cohn ST, Ye F, Belardi JK, Santilli AA, Sabatucci JP, Leiter J, Johnston GH, Bray JA, Burroughs KD, Cosmi SA, Leventhal L, Koury EJ, Zhang Y, Mugford CA, Ho DM, Rosenzweig-Lipson SJ, Platt B, Smith VA, Deecher DC: Structure-activity relationships of the cycloalkanol ethylamine scaffold: discovery of selective norepinephrine reuptake inhibitors. J Med Chem. 2008 Jul 10;51(13):4038-49. doi: 10.1021/jm8002262. Epub 2008 Jun 17. [18557608 ]
  11. Zhang P, Terefenko EA, McComas CC, Mahaney PE, Vu A, Trybulski E, Koury E, Johnston G, Bray J, Deecher D: Synthesis and activity of novel 1- or 3-(3-amino-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones as selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett. 2008 Dec 1;18(23):6067-70. doi: 10.1016/j.bmcl.2008.10.026. Epub 2008 Oct 11. [18951020 ]
  12. Vu AT, Cohn ST, Terefenko EA, Moore WJ, Zhang P, Mahaney PE, Trybulski EJ, Goljer I, Dooley R, Bray JA, Johnston GH, Leiter J, Deecher DC: 3-(Arylamino)-3-phenylpropan-2-olamines as a new series of dual norepinephrine and serotonin reuptake inhibitors. Bioorg Med Chem Lett. 2009 May 1;19(9):2464-7. doi: 10.1016/j.bmcl.2009.03.054. Epub 2009 Mar 18. [19329313 ]
  13. Kim CY, Mahaney PE, McConnell O, Zhang Y, Manas E, Ho DM, Deecher DC, Trybulski EJ: Discovery of a new series of monoamine reuptake inhibitors, the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ols. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5029-32. doi: 10.1016/j.bmcl.2009.07.053. Epub 2009 Jul 23. [19632110 ]
  14. Mahaney PE, Kim CY, Coghlan RD, Cohn ST, Heffernan GD, Huselton CA, Terefenko EA, Vu AT, Zhang P, Burroughs KD, Cosmi SA, Bray JA, Johnston GH, Deecher DC, Trybulski EJ: Structure-activity relationships of the 1-amino-3-(1H-indol-1-yl)-3-phenylpropan-2-ol series of monoamine reuptake inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5807-10. doi: 10.1016/j.bmcl.2009.07.050. Epub 2009 Aug 25. [19713106 ]
  15. Zhang P, Terefenko EA, Bray J, Deecher D, Fensome A, Harrison J, Kim C, Koury E, Mark L, McComas CC, Mugford CA, Trybulski EJ, Vu AT, Whiteside GT, Mahaney PE: 1- or 3-(3-Amino-2-hydroxy-1-phenyl propyl)-1,3-dihydro-2H-benzimidazol-2-ones: potent, selective, and orally efficacious norepinephrine reuptake inhibitors. J Med Chem. 2009 Sep 24;52(18):5703-11. doi: 10.1021/jm900888c. [19722525 ]
  16. Sabatucci JP, Mahaney PE, Leiter J, Johnston G, Burroughs K, Cosmi S, Zhang Y, Ho D, Deecher DC, Trybulski E: Heterocyclic cycloalkanol ethylamines as norepinephrine reuptake inhibitors. Bioorg Med Chem Lett. 2010 May 1;20(9):2809-12. doi: 10.1016/j.bmcl.2010.03.059. Epub 2010 Mar 15. [20378347 ]
  17. O'Neill DJ, Adedoyin A, Bray JA, Deecher DC, Fensome A, Goldberg JA, Harrison J, Leventhal L, Mann C, Mark L, Nogle L, Sullivan NR, Spangler TB, Terefenko EA, Trybulski EJ, Uveges AJ, Vu A, Whiteside GT, Zhang P: Discovery of novel selective norepinephrine inhibitors: 1-(2-morpholin-2-ylethyl)-3-aryl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxides (WYE-114152). J Med Chem. 2011 Oct 13;54(19):6824-31. doi: 10.1021/jm200733r. Epub 2011 Sep 14. [21916421 ]
  18. McComas CC, Vu AT, Mahaney PE, Cohn ST, Fensome A, Marella MA, Nogle L, Trybulski EJ, Ye F, Zhang P, Alfinito P, Bray J, Johnston G, Koury E, Deecher DC: Synthesis and activity of 1-(3-amino-1-phenylpropyl)indolin-2-ones: a new class of selective norepinephrine reuptake inhibitors. Bioorg Med Chem Lett. 2008 Sep 15;18(18):4929-31. doi: 10.1016/j.bmcl.2008.08.060. Epub 2008 Aug 22. [18771916 ]
  19. 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 ]
  20. Heffernan GD, Coghlan RD, Manas ES, McDevitt RE, Li Y, Mahaney PE, Robichaud AJ, Huselton C, Alfinito P, Bray JA, Cosmi SA, Johnston GH, Kenney T, Koury E, Winneker RC, Deecher DC, Trybulski EJ: Dual acting norepinephrine reuptake inhibitors and 5-HT(2A) receptor antagonists: Identification, synthesis and activity of novel 4-aminoethyl-3-(phenylsulfonyl)-1H-indoles. Bioorg Med Chem. 2009 Nov 15;17(22):7802-15. doi: 10.1016/j.bmc.2009.09.023. Epub 2009 Sep 18. [19836247 ]
  21. 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 ]
  22. 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 ]
  23. Schou M, Pike VW, Sovago J, Gulyas B, Gallagher PT, Dobson DR, Walter MW, Rudyk H, Farde L, Halldin C: Synthesis of 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central norepinephrine transporters with PET. Bioorg Med Chem. 2007 Jan 15;15(2):616-25. Epub 2006 Nov 2. [17123820 ]
  24. Deecher DC, Beyer CE, Johnston G, Bray J, Shah S, Abou-Gharbia M, Andree TH: Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther. 2006 Aug;318(2):657-65. Epub 2006 May 4. [16675639 ]
  25. O'Neill DJ, Adedoyin A, Alfinito PD, Bray JA, Cosmi S, Deecher DC, Fensome A, Harrison J, Leventhal L, Mann C, McComas CC, Sullivan NR, Spangler TB, Uveges AJ, Trybulski EJ, Whiteside GT, Zhang P: Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231). J Med Chem. 2010 Jun 10;53(11):4511-21. doi: 10.1021/jm100053t. [20462211 ]
  26. 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 ]
  27. 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 ]
  28. 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:
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
Inhibitory0.0176 uMNot AvailableBindingDB 35229
Inhibitory0.02 uMNot AvailableBindingDB 50010869
Inhibitory0.022 uMNot AvailableBindingDB 35229
Inhibitory0.163 uMNot AvailableBindingDB 35229
Inhibitory0.179 uMNot AvailableBindingDB 35229
IC500.064 uMNot AvailableBindingDB 50010869
IC500.108 uMNot AvailableBindingDB 50010869
IC500.56 uMNot AvailableBindingDB 50010869
References
  1. Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [16140280 ]
  2. Holmes A, Yang RJ, Murphy DL, Crawley JN: Evaluation of antidepressant-related behavioral responses in mice lacking the serotonin transporter. Neuropsychopharmacology. 2002 Dec;27(6):914-23. [12464448 ]
  3. Zhou L, Huang KX, Kecojevic A, Welsh AM, Koliatsos VE: Evidence that serotonin reuptake modulators increase the density of serotonin innervation in the forebrain. J Neurochem. 2006 Jan;96(2):396-406. Epub 2005 Nov 21. [16300628 ]
  4. Hoffman AF, Gerhardt GA: In vivo electrochemical studies of dopamine clearance in the rat substantia nigra: effects of locally applied uptake inhibitors and unilateral 6-hydroxydopamine lesions. J Neurochem. 1998 Jan;70(1):179-89. [9422361 ]
  5. 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 ]
  6. Zhou Z, Zhen J, Karpowich NK, Goetz RM, Law CJ, Reith ME, Wang DN: LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake. Science. 2007 Sep 7;317(5843):1390-3. Epub 2007 Aug 9. [17690258 ]
  7. 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 ]
  8. 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 ]
  9. Altenbach RJ, Black LA, Strakhova MI, Manelli AM, Carr TL, Marsh KC, Wetter JM, Wensink EJ, Hsieh GC, Honore P, Garrison TR, Brioni JD, Cowart MD: Diaryldiamines with dual inhibition of the histamine H(3) receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain. J Med Chem. 2010 Nov 11;53(21):7869-73. doi: 10.1021/jm100666w. [20945906 ]
  10. 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 ]
  11. 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:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
References
  1. Matsumoto K, Ojima K, Ohta H, Watanabe H: Beta 2- but not beta 1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice. Pharmacol Biochem Behav. 1994 Sep;49(1):13-8. [7816863 ]
  2. Sapena R, Morin D, Zini R, Morin C, Tillement JP: Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes. Eur J Pharmacol. 1996 Apr 4;300(1-2):159-62. [8741184 ]
  3. Burgi S, Baltensperger K, Honegger UE: Antidepressant-induced switch of beta 1-adrenoceptor trafficking as a mechanism for drug action. J Biol Chem. 2003 Jan 10;278(2):1044-52. Epub 2002 Oct 21. [12393876 ]
  4. Samnick S, Scheuer C, Munks S, El-Gibaly AM, Menger MD, Kirsch CM: Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4-(2-mercapto-2-methylprop ylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats. Nucl Med Biol. 2004 May;31(4):511-22. [15093822 ]
  5. Mudunkotuwa NT, Horton RW: Desipramine administration in the olfactory bulbectomized rat: changes in brain beta-adrenoceptor and 5-HT2A binding sites and their relationship to behaviour. Br J Pharmacol. 1996 Apr;117(7):1481-6. [8730743 ]
General Function:
Protein homodimerization activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine.
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular Weight:
46458.32 Da
References
  1. Matsumoto K, Ojima K, Ohta H, Watanabe H: Beta 2- but not beta 1-adrenoceptors are involved in desipramine enhancement of aggressive behavior in long-term isolated mice. Pharmacol Biochem Behav. 1994 Sep;49(1):13-8. [7816863 ]
  2. Sapena R, Morin D, Zini R, Morin C, Tillement JP: Desipramine treatment differently down-regulates beta-adrenoceptors of freshly isolated neurons and astrocytes. Eur J Pharmacol. 1996 Apr 4;300(1-2):159-62. [8741184 ]
  3. Abadie C, Foucart S, Page P, Nadeau R: Modulation of noradrenaline release from isolated human atrial appendages. J Auton Nerv Syst. 1996 Dec 14;61(3):269-76. [8988485 ]
  4. Prenner L, Sieben A, Zeller K, Weiser D, Haberlein H: Reduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy. Biochemistry. 2007 May 1;46(17):5106-13. Epub 2007 Apr 7. [17417877 ]
  5. Osadchii OE, Woodiwiss AJ, Deftereos D, Norton GR: Temporal changes in myocardial adrenergic regulation with the progression to pump dysfunction after chronic beta-adrenoreceptor activation in rats. Pflugers Arch. 2007 Nov;455(2):251-60. Epub 2007 Jun 9. [17558518 ]
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
Inhibitory3 uMNot AvailableBindingDB 50010869
Inhibitory3.19 uMNot AvailableBindingDB 35229
Inhibitory>10 uMNot AvailableBindingDB 35229
IC5047.9 uMNot AvailableBindingDB 50010869
IC5082 uMNot AvailableBindingDB 50010869
References
  1. Zhou Z, Zhen J, Karpowich NK, Goetz RM, Law CJ, Reith ME, Wang DN: LeuT-desipramine structure reveals how antidepressants block neurotransmitter reuptake. Science. 2007 Sep 7;317(5843):1390-3. Epub 2007 Aug 9. [17690258 ]
  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. Carroll FI, Howell LL, Kuhar MJ: Pharmacotherapies for treatment of cocaine abuse: preclinical aspects. J Med Chem. 1999 Jul 29;42(15):2721-36. [10425082 ]
  4. 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 ]
  5. 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:
Sphingomyelin phosphodiesterase activity
Specific Function:
Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic activity.
Gene Name:
SMPD1
Uniprot ID:
P17405
Molecular Weight:
69751.3 Da
References
  1. Testai FD, Landek MA, Dawson G: Regulation of sphingomyelinases in cells of the oligodendrocyte lineage. J Neurosci Res. 2004 Jan 1;75(1):66-74. [14689449 ]
  2. Kolzer M, Werth N, Sandhoff K: Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine. FEBS Lett. 2004 Feb 13;559(1-3):96-8. [14960314 ]
  3. Erdreich-Epstein A, Tran LB, Cox OT, Huang EY, Laug WE, Shimada H, Millard M: Endothelial apoptosis induced by inhibition of integrins alphavbeta3 and alphavbeta5 involves ceramide metabolic pathways. Blood. 2005 Jun 1;105(11):4353-61. Epub 2005 Feb 10. [15705795 ]
  4. Zeidan YH, Pettus BJ, Elojeimy S, Taha T, Obeid LM, Kawamori T, Norris JS, Hannun YA: Acid ceramidase but not acid sphingomyelinase is required for tumor necrosis factor-{alpha}-induced PGE2 production. J Biol Chem. 2006 Aug 25;281(34):24695-703. Epub 2006 Jun 27. [16803890 ]
  5. Hurwitz R, Ferlinz K, Sandhoff K: The tricyclic antidepressant desipramine causes proteolytic degradation of lysosomal sphingomyelinase in human fibroblasts. Biol Chem Hoppe Seyler. 1994 Jul;375(7):447-50. [7945993 ]
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
Inhibitory0.066 uMNot AvailableBindingDB 35229
Inhibitory0.54 uMNot AvailableBindingDB 35229
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  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. 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:
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
Inhibitory0.06 uMNot AvailableBindingDB 35229
Inhibitory0.12 uMNot AvailableBindingDB 35229
References
  1. Sawynok J, Esser MJ, Reid AR: Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain. 1999 Aug;82(2):149-58. [10467920 ]
  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. 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
Inhibitory0.11 uMNot AvailableBindingDB 35229
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  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:
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
IC501.38038 uMNot AvailableBindingDB 50010869
IC501.514 uMNot AvailableBindingDB 50010869
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
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
Inhibitory6.4 uMNot AvailableBindingDB 35229
Inhibitory>10 uMNot AvailableBindingDB 35229
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. 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:
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
Inhibitory0.16 uMNot AvailableBindingDB 50010869
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. 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
Inhibitory0.35 uMNot AvailableBindingDB 35229
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. 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:
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
Inhibitory1.379 uMNot AvailableBindingDB 35229
Inhibitory5.5 uMNot AvailableBindingDB 35229
References
  1. 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 ]
  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 ]
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
Inhibitory0.21 uMNot AvailableBindingDB 35229
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
Inhibitory0.16 uMNot AvailableBindingDB 35229
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 ]
17. Alpha-1 adrenergic receptors (Protein Group)
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.
Included Proteins:
P35348 , P35368 , P25100
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 ]
18. Alpha-2 adrenergic receptors (Protein Group)
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.
Included Proteins:
P08913 , P18089 , P18825
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:
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
Inhibitory5.465 uMNot AvailableBindingDB 35229
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
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:
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
IC503.8 uMNot AvailableBindingDB 50010869
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:
Histamine receptor activity
Specific Function:
The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization.
Gene Name:
HRH3
Uniprot ID:
Q9Y5N1
Molecular Weight:
48670.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>5 uMNot AvailableBindingDB 50010869
References
  1. Altenbach RJ, Black LA, Strakhova MI, Manelli AM, Carr TL, Marsh KC, Wetter JM, Wensink EJ, Hsieh GC, Honore P, Garrison TR, Brioni JD, Cowart MD: Diaryldiamines with dual inhibition of the histamine H(3) receptor and the norepinephrine transporter and the efficacy of 4-(3-(methylamino)-1-phenylpropyl)-6-(2-(pyrrolidin-1-yl)ethoxy)naphthalen-1-ol in pain. J Med Chem. 2010 Nov 11;53(21):7869-73. doi: 10.1021/jm100666w. [20945906 ]
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:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation851.138 uMNot AvailableBindingDB 50010869
References
  1. Lazaro E, Lowe PJ, Briand X, Faller B: New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin. J Med Chem. 2008 Apr 10;51(7):2009-17. doi: 10.1021/jm7012826. Epub 2008 Mar 19. [18348514 ]
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
IC5056.8 uMNot AvailableBindingDB 50010869
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 ]