You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2009-07-21 20:28:22 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2985
Identification
Common NameSertraline
ClassSmall Molecule
DescriptionSertraline hydrochloride belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs). Despite distinct structural differences between compounds in this class, SSRIs possess similar pharmacological activity. As with other antidepressant agents, several weeks of therapy may be required before a clinical effect is seen. SSRIs are potent inhibitors of neuronal serotonin reuptake. They have little to no effect on norepinephrine or dopamine reuptake and do not antagonize α- or β-adrenergic, dopamine D2 or histamine H1 receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT1A and terminal autoreceptors. The overall clinical effect of increased mood and decreased anxiety is thought to be due to adaptive changes in neuronal function that leads to enhanced serotonergic neurotransmission. Side effects include dry mouth, nausea, dizziness, drowsiness, sexual dysfunction and headache (see Toxicity section below for a more detailed listing of side effects). Compared to other agents in this class, sertraline may cause greater diarrheal and male sexual dysfunction effects. Side effects generally occur within the first two weeks of therapy and are usually less severe and frequent than those observed with tricyclic antidepressants. Sertraline may be used to treat major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD) and social anxiety disorder (social phobia).
Compound Type
  • Amine
  • Antidepressant
  • Antidepressive Agent
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Selective Serotonin Reuptake Inhibitor
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Sertraline
(1S,4S)-Sertraline
(1S-cis)-1,2,3,4-Tetrahydro-4-(3,4-dichlorophenyl)-N-methyl-1-naphthalenamine
Apo-Sertraline
cis-(+)-Sertraline
CP 51974
Lustral
Sertralina
Sertraline hydrochloride
Sertralinum
Zoloft
Chemical FormulaC17H17Cl2N
Average Molecular Mass306.230 g/mol
Monoisotopic Mass305.074 g/mol
CAS Registry Number79617-96-2
IUPAC Name(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine
Traditional Namesertraline
SMILES[H][C@@]1(CC[C@@]([H])(C2=CC(Cl)=C(Cl)C=C2)C2=CC=CC=C12)NC
InChI IdentifierInChI=1S/C17H17Cl2N/c1-20-17-9-7-12(13-4-2-3-5-14(13)17)11-6-8-15(18)16(19)10-11/h2-6,8,10,12,17,20H,7,9H2,1H3/t12-,17-/m0/s1
InChI KeyInChIKey=VGKDLMBJGBXTGI-SJCJKPOMSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tametralines. Tametralines are compounds containing a tametraline moiety, which consists of a tetrahydronaphthalene linked to a phenyl group to form N-methyl-4-phenyl-1,2,3,4-tetrahydronaphthalen-1-amine skeleton.
KingdomOrganic compounds
Super ClassBenzenoids
ClassTetralins
Sub ClassTametralines
Direct ParentTametralines
Alternative Parents
Substituents
  • Tametraline
  • 1,2-dichlorobenzene
  • Chlorobenzene
  • Halobenzene
  • Aralkylamine
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Secondary aliphatic amine
  • Secondary amine
  • Organohalogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic nitrogen compound
  • Amine
  • Organochloride
  • Organonitrogen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Liver
  • Platelet
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point243-245°C
Boiling PointNot Available
Solubility3.5mg/L
LogP5.1
Predicted Properties
PropertyValueSource
Water Solubility0.00014 g/LALOGPS
logP5.06ALOGPS
logP5.15ChemAxon
logS-6.3ALOGPS
pKa (Strongest Basic)9.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity85.74 m³·mol⁻¹ChemAxon
Polarizability32.44 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-004j-0490000000-724d07a27d5e8d538495JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0091000000-10f81c7fd0a8c096039dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-056r-0980000000-58873180fd0c95a215b3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0bt9-0900000000-35c397f9293e114f3234JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0900000000-569e7b0694b3ef81cf90JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-056r-0970000000-2de49c544ebd922028dcJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-056r-0970000000-7753c869949091f5c066JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-056r-0970000000-a995c3f140efa6578777JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0bt9-2900000000-dee4675a5062129266c9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a6r-0950000000-2a9cba59b69c41b10a59JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0139000000-4f4b68d5ff5484e81ce9JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-1779000000-742a47a4d5d21cc8acb1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03xr-1960000000-f03bdc5054705000574cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-d658426c80474367477aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-0029000000-68fb5194b39f7a3d992bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0kwo-4390000000-925d4346a5a2a057e466JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-00b9-2890000000-d53a90b04ec8457ad2f1JSpectraViewer | MoNA
Toxicity Profile
Route of ExposureThe effects of food on the bioavailability of the sertraline tablet and oral concentrate were studied in subjects administered a single dose with and without food. For the tablet, AUC was slightly increased when drug was administered with food but the Cmax was 25% greater, while the time to reach peak plasma concentration (Tmax) decreased from 8 hours post-dosing to 5.5 hours. For the oral concentrate, Tmax was slightly prolonged from 5.9 hours to 7.0 hours with food.
Mechanism of ToxicityThe exact mechanism of action sertraline is not fully known, but the drug appears to selectively inhibit the reuptake of serotonin at the presynaptic membrane. This results in an increased synaptic concentration of serotonin in the CNS, which leads to numerous functional changes associated with enhanced serotonergic neurotransmission. It is suggested that these modifications are responsible for the antidepressant action observed during long term administration of antidepressants. It has also been hypothesized that obsessive-compulsive disorder is caused by the dysregulation of serotonin, as it is treated by sertraline, and the drug corrects this imbalance.
MetabolismExtensively metabolized in the liver. Sertraline metabolism involves N-demethylation, N-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid. Sertraline undergoes N-demethylation primarily catalyzed by cytochrome P450 (CYP) 2B6, with CYP2C19, CYP3A4 and CYP2D6 contributing to a lesser extent. Deamination occurs via CYP3A4 and CYP2C19. In vitro studies have shown that monoamine oxidase A and B may also catalyze sertraline deamination. Sertraline N-carbamoyl glucuronidation has also been observed in human liver microsomes. Route of Elimination: Sertraline is extensively metabolized and excretion of unchanged drug in urine is a minor route of elimination. Half Life: The elimination half-life of sertraline is approximately 25-26 hours. The elimination half-life of desmethylsertraline is approximately 62-104 hours.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the management of major depressive disorder, posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder with or without agoraphobia, premenstrual dysphoric disorder, social phobia, premature ejaculation, and vascular headaches.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of toxicity include alopecia, decreased libido, diarrhea, ejaculation disorder, fatigue, insomnia, somnolence and serotonin syndrome.
TreatmentTreatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Due to large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit. No specific antidotes for sertraline are known. (19)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01104
HMDB IDHMDB05010
PubChem Compound ID68617
ChEMBL IDCHEMBL809
ChemSpider ID61881
KEGG IDC07246
UniProt IDNot Available
OMIM ID
ChEBI ID9123
BioCyc IDNot Available
CTD IDNot Available
Stitch IDSertraline
PDB IDSRE
ACToR IDNot Available
Wikipedia LinkSertraline
References
Synthesis Reference

George J. Quallich, Michael T. Williams, “Process for preparing sertraline intermediates.” U.S. Patent US4839104, issued February, 1977.

MSDST3D2985.pdf
General References
  1. Couzin J: The brains behind blockbusters. Science. 2005 Jul 29;309(5735):728. [16051786 ]
  2. Fabre LF, Abuzzahab FS, Amin M, Claghorn JL, Mendels J, Petrie WM, Dube S, Small JG: Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo. Biol Psychiatry. 1995 Nov 1;38(9):592-602. [8573661 ]
  3. Kronig MH, Apter J, Asnis G, Bystritsky A, Curtis G, Ferguson J, Landbloom R, Munjack D, Riesenberg R, Robinson D, Roy-Byrne P, Phillips K, Du Pont IJ: Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder. J Clin Psychopharmacol. 1999 Apr;19(2):172-6. [10211919 ]
  4. Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, Farfel GM: Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA. 2000 Apr 12;283(14):1837-44. [10770145 ]
  5. Yonkers KA, Halbreich U, Freeman E, Brown C, Endicott J, Frank E, Parry B, Pearlstein T, Severino S, Stout A, Stone A, Harrison W: Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group. JAMA. 1997 Sep 24;278(12):983-8. [9307345 ]
  6. Shelton RC: The role of sertraline in the management of depression. Clin Ther. 1994 Sep-Oct;16(5):768-82; discussion 767. [7859236 ]
  7. Murdoch D, McTavish D: Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs. 1992 Oct;44(4):604-24. [1281075 ]
  8. Agnel M, Esnaud H, Langer SZ, Graham D: Pharmacological characterization of the cloned human 5-hydroxytryptamine transporter. Biochem Pharmacol. 1996 May 3;51(9):1145-51. [8645336 ]
  9. Serebruany VL, Suckow RF, Cooper TB, O'Connor CM, Malinin AI, Krishnan KR, van Zyl LT, Lekht V, Glassman AH: Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression. Am J Psychiatry. 2005 Jun;162(6):1165-70. [15932816 ]
  10. Parsey RV, Kent JM, Oquendo MA, Richards MC, Pratap M, Cooper TB, Arango V, Mann JJ: Acute occupancy of brain serotonin transporter by sertraline as measured by [11C]DASB and positron emission tomography. Biol Psychiatry. 2006 May 1;59(9):821-8. Epub 2005 Oct 6. [16213473 ]
  11. Markovitz JH, Shuster JL, Chitwood WS, May RS, Tolbert LC: Platelet activation in depression and effects of sertraline treatment: An open-label study. Am J Psychiatry. 2000 Jun;157(6):1006-8. [10831484 ]
  12. Obach RS, Cox LM, Tremaine LM: Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos. 2005 Feb;33(2):262-70. Epub 2004 Nov 16. [15547048 ]
  13. Epperson CN, Jatlow PI, Czarkowski K, Anderson GM: Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs. Pediatrics. 2003 Nov;112(5):e425. [14595087 ]
  14. Serebruany VL, Gurbel PA, O'Connor CM: Platelet inhibition by sertraline and N-desmethylsertraline: a possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol Res. 2001 May;43(5):453-62. [11394937 ]
  15. Kobayashi K, Yamamoto T, Chiba K, Tani M, Ishizaki T, Kuroiwa Y: The effects of selective serotonin reuptake inhibitors and their metabolites on S-mephenytoin 4'-hydroxylase activity in human liver microsomes. Br J Clin Pharmacol. 1995 Nov;40(5):481-5. [8703653 ]
  16. Phillips OM, Wood KM, Williams DC: Kinetics of the interaction of sertraline with the human platelet plasma membrane 5-hydroxytryptamine carrier. Eur J Pharmacol. 1988 Feb 9;146(2-3):299-306. [3371401 ]
  17. Pivac N, Muck-Seler D, Sagud M, Jakovljevic M, Mustapic M, Mihaljevic-Peles A: Long-term sertraline treatment and peripheral biochemical markers in female depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Aug;27(5):759-65. [12921906 ]
  18. Drugs.com [Link]
  19. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
IC500.31 uMNot AvailableBindingDB 50028094
Dissociation0.025 uMNot AvailableBindingDB 50028094
References
  1. 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 ]
  2. Ghanizadeh A: Sertraline-associated hair loss. J Drugs Dermatol. 2008 Jul;7(7):693-4. [18664165 ]
  3. Lemke MR: [Antidepressant effects of dopamine agonists. Experimental and clinical findings]. Nervenarzt. 2007 Jan;78(1):31-8. [17187269 ]
  4. Nemeroff CB, Owens MJ: Pharmacologic differences among the SSRIs: focus on monoamine transporters and the HPA axis. CNS Spectr. 2004 Jun;9(6 Suppl 4):23-31. [15181382 ]
  5. Goodnick PJ, Goldstein BJ: Selective serotonin reuptake inhibitors in affective disorders--I. Basic pharmacology. J Psychopharmacol. 1998;12(3 Suppl B):S5-20. [9808077 ]
  6. Carlier PR, Lo MM, Lo PC, Richelson E, Tatsumi M, Reynolds IJ, Sharma TA: Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group. Bioorg Med Chem Lett. 1998 Mar 3;8(5):487-92. [9871604 ]
  7. Middleton DS, Andrews M, Glossop P, Gymer G, Jessiman A, Johnson PS, Mackenny M, Pitcher MJ, Rooker T, Stobie A, Tang K, Morgan P: Designing rapid onset selective serotonin re-uptake inhibitors. Part 1: Structure-activity relationships of substituted (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthaleneamine. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1434-9. Epub 2005 Nov 28. [16314097 ]
  8. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]
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
IC500.003 uMNot AvailableBindingDB 50028094
Dissociation0.00029 uMNot AvailableBindingDB 50028094
References
  1. Benmansour S, Cecchi M, Morilak DA, Gerhardt GA, Javors MA, Gould GG, Frazer A: Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level. J Neurosci. 1999 Dec 1;19(23):10494-501. [10575045 ]
  2. Benmansour S, Owens WA, Cecchi M, Morilak DA, Frazer A: Serotonin clearance in vivo is altered to a greater extent by antidepressant-induced downregulation of the serotonin transporter than by acute blockade of this transporter. J Neurosci. 2002 Aug 1;22(15):6766-72. [12151556 ]
  3. Borkowska A, Pilaczynska E, Araszkiewicz A, Rybakowski J: [The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder]. Psychiatr Pol. 2002 Nov-Dec;36(6 Suppl):289-95. [12647451 ]
  4. Durham LK, Webb SM, Milos PM, Clary CM, Seymour AB: The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder. Psychopharmacology (Berl). 2004 Aug;174(4):525-9. Epub 2003 Sep 4. [12955294 ]
  5. Chen F, Larsen MB, Neubauer HA, Sanchez C, Plenge P, Wiborg O: Characterization of an allosteric citalopram-binding site at the serotonin transporter. J Neurochem. 2005 Jan;92(1):21-8. [15606893 ]
  6. Carlier PR, Lo MM, Lo PC, Richelson E, Tatsumi M, Reynolds IJ, Sharma TA: Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group. Bioorg Med Chem Lett. 1998 Mar 3;8(5):487-92. [9871604 ]
  7. Middleton DS, Andrews M, Glossop P, Gymer G, Jessiman A, Johnson PS, Mackenny M, Pitcher MJ, Rooker T, Stobie A, Tang K, Morgan P: Designing rapid onset selective serotonin re-uptake inhibitors. Part 1: Structure-activity relationships of substituted (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthaleneamine. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1434-9. Epub 2005 Nov 28. [16314097 ]
  8. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]
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
References
  1. David DJ, Bourin M, Hascoet M, Colombel MC, Baker GB, Jolliet P: Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice. Psychopharmacology (Berl). 2001 Feb;153(4):443-9. [11243491 ]
  2. Fornal CA, Metzler CW, Mirescu C, Stein SK, Jacobs BL: Effects of standardized extracts of St. John's wort on the single-unit activity of serotonergic dorsal Raphe neurons in awake cats: comparisons with fluoxetine and sertraline. Neuropsychopharmacology. 2001 Dec;25(6):858-70. [11750179 ]
  3. Rossi DV, Valdez M, Gould GG, Hensler JG: Chronic administration of venlafaxine fails to attenuate 5-HT1A receptor function at the level of receptor-G protein interaction. Int J Neuropsychopharmacol. 2006 Aug;9(4):393-406. Epub 2005 Jul 22. [16035959 ]
  4. Rogoz Z, Skuza G: Mechanism of synergistic action following co-treatment with pramipexole and fluoxetine or sertraline in the forced swimming test in rats. Pharmacol Rep. 2006 Jul-Aug;58(4):493-500. [16963794 ]
  5. Darmani NA, Reeves SL: The stimulatory and inhibitory components of cocaine's actions on the 5-HTP-induced 5-HT2A receptor response. Pharmacol Biochem Behav. 1996 Nov;55(3):387-96. [8951980 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Rasmussen BB, Brosen K: Is therapeutic drug monitoring a case for optimizing clinical outcome and avoiding interactions of the selective serotonin reuptake inhibitors? Ther Drug Monit. 2000 Apr;22(2):143-54. [10774624 ]
  2. Rojdmark S, von Bahr C: [Metabolic interaction between psychopharmaceuticals. Probable cause of exacerbation of hypothyroidism according to a case report]. Lakartidningen. 2002 Jun 20;99(25):2854-6. [12143142 ]
  3. DeVane CL, Donovan JL, Liston HL, Markowitz JS, Cheng KT, Risch SC, Willard L: Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 2004 Feb;24(1):4-10. [14709940 ]
  4. Obach RS, Cox LM, Tremaine LM: Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos. 2005 Feb;33(2):262-70. Epub 2004 Nov 16. [15547048 ]
  5. Alderman J: Coadministration of sertraline with cisapride or pimozide: an open-label, nonrandomized examination of pharmacokinetics and corrected QT intervals in healthy adult volunteers. Clin Ther. 2005 Jul;27(7):1050-63. [16154484 ]
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
IC500.825 uMNot AvailableBindingDB 50028094
Dissociation0.42 uMNot AvailableBindingDB 50028094
References
  1. Carlier PR, Lo MM, Lo PC, Richelson E, Tatsumi M, Reynolds IJ, Sharma TA: Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional group. Bioorg Med Chem Lett. 1998 Mar 3;8(5):487-92. [9871604 ]
  2. Middleton DS, Andrews M, Glossop P, Gymer G, Jessiman A, Johnson PS, Mackenny M, Pitcher MJ, Rooker T, Stobie A, Tang K, Morgan P: Designing rapid onset selective serotonin re-uptake inhibitors. Part 1: Structure-activity relationships of substituted (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthaleneamine. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1434-9. Epub 2005 Nov 28. [16314097 ]
  3. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.31 uMNot AvailableBindingDB 50028094
References
  1. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>10 uMNot AvailableBindingDB 50028094
References
  1. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.4 uMNot AvailableBindingDB 50028094
References
  1. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.8 uMNot AvailableBindingDB 50028094
References
  1. Shao L, Wang F, Malcolm SC, Ma J, Hewitt MC, Campbell UC, Bush LR, Spicer NA, Engel SR, Saraswat LD, Hardy LW, Koch P, Schreiber R, Spear KL, Varney MA: Synthesis and pharmacological evaluation of 4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalenyl amines as triple reuptake inhibitors. Bioorg Med Chem. 2011 Jan 1;19(1):663-76. doi: 10.1016/j.bmc.2010.10.034. Epub 2010 Oct 21. [21093273 ]