Sertraline
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Basic Info
| Common Name | Sertraline(F04783) |
| 2D Structure | |
| Description | Sertraline 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 D<sub>2</sub> or histamine H<sub>1</sub> receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT<sub>1A</sub> and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT<sub>1A</sub> 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). |
| FRCD ID | F04783 |
| CAS Number | 79617-96-2 |
| PubChem CID | 68617 |
| Formula | C17H17Cl2N |
| IUPAC Name | (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine |
| InChI Key | VGKDLMBJGBXTGI-SJCJKPOMSA-N |
| InChI | InChI=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 |
| Canonical SMILES | CNC1CCC(C2=CC=CC=C12)C3=CC(=C(C=C3)Cl)Cl |
| Isomeric SMILES | CN[C@H]1CC[C@H](C2=CC=CC=C12)C3=CC(=C(C=C3)Cl)Cl |
| Wikipedia | Sertraline |
| Synonyms |
(1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine
sertraline
79617-96-2
Sertralina
Sertralinum
(+)-Sertraline
Lustral
Zoloft
Sertralinum [Latin]
Sertralina [Spanish]
|
| Classifies |
Predicted: Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Tetralins |
| Subclass | Tametralines |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Tametralines |
| Alternative Parents | |
| Molecular Framework | Aromatic homopolycyclic compounds |
| 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 |
| Description | This compound belongs to the class of organic compounds known as tametralines. These 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 306.23 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 2 |
| Complexity | 322 |
| Monoisotopic Mass | 305.074 |
| Exact Mass | 305.074 |
| XLogP | 4.8 |
| Formal Charge | 0 |
| Heavy Atom Count | 20 |
| Defined Atom Stereocenter Count | 2 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9713 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.6995 |
| P-glycoprotein Substrate | Non-substrate | 0.5858 |
| P-glycoprotein Inhibitor | Inhibitor | 0.7333 |
| Non-inhibitor | 0.8319 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.6726 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.7870 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7100 |
| CYP450 2D6 Substrate | Substrate | 0.8918 |
| CYP450 3A4 Substrate | Substrate | 0.6304 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.7909 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9307 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.6469 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.6839 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.5442 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.6633 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9151 |
| Inhibitor | 0.7185 | |
| AMES Toxicity | AMES toxic | 0.5353 |
| Carcinogens | Non-carcinogens | 0.8499 |
| Fish Toxicity | High FHMT | 0.9916 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9971 |
| Honey Bee Toxicity | Low HBT | 0.7146 |
| Biodegradation | Not ready biodegradable | 0.9522 |
| Acute Oral Toxicity | III | 0.4808 |
| Carcinogenicity (Three-class) | Non-required | 0.7805 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.9452 | LogS |
| Caco-2 Permeability | 1.5931 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.5020 | LD50, mol/kg |
| Fish Toxicity | 0.8121 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.9909 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Identification of Combinations of Approved Drugs With Synergistic ActivityAgainst Ebola Virus in Cell Cultures. | J Infect Dis | 2018 Jun 25 | 29939303 |
| Treatment with high-dose antidepressants severely exacerbates the pathologicaloutcome of experimental Escherichia coli infections in poultry. | PLoS One | 2017 Oct 11 | 29020098 |
| Physicochemical analysis and nonisothermal kinetic study of sertraline-lactosebinary mixtures. | J Food Drug Anal | 2017 Jul | 28911656 |
| Kynurenine 3-monooxygenase is implicated in antidepressants-responsivedepressive-like behaviors and monoaminergic dysfunctions. | Behav Brain Res | 2017 Jan 15 | 27693848 |
| A Positive Allosteric Modulator of the Serotonin 5-HT2C Receptor for Obesity. | J Med Chem | 2017 Dec 14 | 29116785 |
| Treatment with TREK1 and TRPC3/6 ion channel inhibitors upregulates microRNAexpression in a mouse model of chronic mild stress. | Neurosci Lett | 2017 Aug 24 | 28716528 |
| Orexin signaling is necessary for hypoglycemia-induced prevention of conditioned place preference. | Am J Physiol Regul Integr Comp Physiol | 2016 Jan 1 | 26511522 |
| A screen of approved drugs and molecular probes identifies therapeutics withanti-Ebola virus activity. | Sci Transl Med | 2015 Jun 3 | 26041706 |
| Chromium supplementation for menstrual cycle-related mood symptoms. | J Diet Suppl | 2013 Dec | 24237190 |
| Qualitative screening for adulterants in weight-loss supplements by ion mobility spectrometry. | J Pharm Biomed Anal | 2012 Dec | 22902504 |
| Anhedonia in postpartum rats. | Physiol Behav | 2010 Jan 12 | 19850056 |
| [Zinc involvements in the brain]. | Rev Med Chir Soc Med Nat Iasi | 2007 Oct-Dec | 18389791 |
| Drug interactions with cisapride: clinical implications. | Clin Pharmacokinet | 2000 Jul | 10926350 |
| Toxic optic neuropathy after concomitant use of melatonin, zoloft, and a high-protein diet. | J Neuroophthalmol | 1999 Dec | 10608673 |
| Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in5 patients. | J Clin Psychiatry | 1999 Apr | 10221284 |
| Preclinical toxicological evaluation of sertraline hydrochloride. | Drug Chem Toxicol | 1998 Nov | 10048942 |
| Preclinical toxicological evaluation of sertraline hydrochloride. | Drug Chem Toxicol | 1998 May | 9598298 |
Targets
- Uniprot ID:
- P05184
- Mechanism of Action:
- It is believed that sertraline inhibits reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because of decreased binding to histamine, acetylcholine, and norepinephrine receptors.
References
- 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 ]
- 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
References
- 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 ]
- 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
References
- 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
References
- 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
References
- 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:
- 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
References
- Lemke MR: [Antidepressant effects of dopamine agonists. Experimental and clinical findings]. Nervenarzt. 2007 Jan;78(1):31-8. [17187269 ]
- 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
- Mechanism of Action:
- It is believed that sertraline inhibits reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because of decreased binding to histamine, acetylcholine, and norepinephrine receptors.
References
- 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 ]
- 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
- Mechanism of Action:
- It is believed that sertraline inhibits reuptake of serotonin at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because of decreased binding to histamine, acetylcholine, and norepinephrine receptors.
References
- 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 ]
- 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
References
- 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 ]