3027 Sertraline 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 &alpha;- or &beta;-adrenergic, dopamine D₂ or histamine H₁ receptors. During acute use, SSRIs block serotonin reuptake and increase serotonin stimulation of somatodendritic 5-HT_1A and terminal autoreceptors. Chronic use leads to desensitization of somatodendritic 5-HT_1A 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). 79617-96-2 68617 C17H17Cl2N 305.073800 White powder. 243-245°C 3.5mg/L The 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. The 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. Extensively metabolized in the liver. Sertraline metabolism involves <i>N</i>-demethylation, <i>N</i>-hydroxylation, oxidative deamination, and glucuronidation of sertraline carbamic acid. Sertraline undergoes <i>N</i>-demethylation primarily catalyzed by cytochrome P450 (CYP) 2B6, with CYP2C19, CYP3A4 and CYP2D6 contributing to a lesser extent. Deamination occurs via CYP3A4 and CYP2C19. <i>In vitro</i> studies have shown that monoamine oxidase A and B may also catalyze sertraline deamination. Sertraline <i>N</i>-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. No indication of carcinogenicity to humans (not listed by IARC). For 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. Symptoms of toxicity include alopecia, decreased libido, diarrhea, ejaculation disorder, fatigue, insomnia, somnolence and serotonin syndrome. Treatment 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. (L1712) 2009-07-21T20:28:22Z 2026-05-14T16:57:51Z Sertraline C07246 9123 Sertraline DB01104 SRE true CN[C@H]1CC[C@@H](C2=CC(Cl)=C(Cl)C=C2)C2=CC=CC=C12 C17H17Cl2N 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 VGKDLMBJGBXTGI-SJCJKPOMSA-N 306.23 305.073804963 Exogenous Solid 5.1 HMDB05010 CHEMBL809 61881 <p>George J. Quallich, Michael T. Williams, &#8220;Process for preparing sertraline intermediates.&#8221; U.S. Patent US4839104, issued February, 1977.</p> CHEM002346 DTXSID6023577 NS00000030 (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine 12.03 85.741 32.442850025091104 2 1 1 9.853307918944921 1 3 5.06 -6.32 1.45e-04 g/l