Selrotine Mechanism of Action

Pharmacology: Pharmacodynamics: Sertraline, a selective serotonin-reuptake inhibitor (SSRI) antidepressant agent, is a naphthalenamine-derivative. It has been shown to selectively inhibit the reuptake of serotonin at the presynaptic neuronal membrane. Sertraline-induced inhibition of serotonin reuptake causes increased synaptic concentrations of serotonin in the CNS. In animal studies, long-term administration of Sertraline has been shown to downregulate noradrenergic receptors in the CNS. Sertraline appears to have only very weak effects on the reuptake of norepinephrine or dopamine and does not possess clinically important affinity for adrenergic (α₁, α₂, β), histaminergic, muscarinic, GABA, benzodiazepine, or dopamine receptors.
In animal studies, Sertraline has effects on sleep cycle by suppressing rapid eye movement (REM) sleep stage. It possesses anorexigenic activity. Sertraline does not appear to cause clinically important sedation and does not interfere with psychomotor performance.
Pharmacokinetics: Sertraline appears to be slowly but well absorbed from the GI tract following oral administration. Administration of a single dose of Sertraline tablet with food increases peak plasma concentrations approximately 25% and decreases the time to achieve peak plasma concentrations from 8 to 5.5 hours, but such changes do not appear to be clinically important. Peak plasma Sertraline concentrations are proportional and linearly related to dose which usually occur within 4.5-8.4 hours following oral administration of 50-200 mg once daily for 14 days.
Following multiple dosing, steady state plasma Sertraline concentrations should be achieved after approximately a week of once-daily dosing. Plasma clearance was approximately 40% lower in elderly patients. Therefore, steady state should be achieved after 2 to 3 weeks in elder patients.
When compared with single dose, there is an approximate two-fold accumulation of Sertraline after multiple daily dosing in dosage ranging from 50-200 mg daily.
Sertraline is approximately 98% bound to plasma proteins. Sertraline undergoes extensive first-pass metabolism in the liver to its mainly metabolite, N-desmethylsertraline via N-demethylation. Data from in vivo and in vitro studies have shown that N-desmethylsertraline is approximately 5-10 times less potent as an inhibitor of serotonin reuptake than Sertraline. Both Sertraline and N-desmethylsertraline are widely distributed in body tissues. Sertraline crosses the blood-brain barrier in human. Both Sertraline and N-desmethylsertraline are distributed into milk.
The elimination half-life of Sertraline and N-desmethylsertraline are 26 hours and 62-104 hours, respectively.
Sertraline and its metabolites are excreted in about equal amounts, approximately 40-45% in both urine and feces (12-14% of unchanged Sertraline was excreted in feces).