化合物信息

Drug Groups

approved

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 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).

Indication

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.

Pharmacology

Sertraline, an antidepressant drug similar to citalopram, fluoxetine, and paroxetine, is of the selective serotonin reuptake inhibitor (SSRI) type. Sertraline has one active metabolite and, like the other SSRIs, have less sedative, anticholinergic, and cardiovascular effects than the tricyclic antidepressant drugs because it does not have clinically important anticholinergic, antihistamine, or adrenergic blocking activity.

Toxicity

Symptoms of toxicity include alopecia, decreased libido, diarrhea, ejaculation disorder, fatigue, insomnia, somnolence and serotonin syndrome. The most frequently observed side effects include: GI effects such as nausea, diarrhea or loose stools, dyspepsia, and dry mouth; nervous system effects such as somnolence, dizziness, insomnia, and tremor; sexual dysfunction in males (principally ejaculatory delay); and sweating.

Affected Organisms

Biotransformation

Extensively 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.

Absorption

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.

Half Life

The elimination half-life of sertraline is approximately 25-26 hours. The elimination half-life of desmethylsertraline is approximately 62-104 hours.

Protein Binding

98% bound to serum proteins, principally to albumin and α₁-acid glycoprotein

Elimination

Sertraline is extensively metabolized and excretion of unchanged drug in urine is a minor route of elimination.

References

External Links