Mechanism of Action
Sertraline is primarily a serotonin reuptake inhibitor (SRI), with a binding affinity (Ki) of 3.3 nM. Therapeutic doses of sertraline (50–200 mg/day) taken by patients for four weeks resulted in 80–90% inhibition of serotonin transporter (SERT) in striatum as measured by positron emission tomography. A daily 9 mg dose was sufficient to inhibit 50% of SERT.
Sertraline is also a dopamine reuptake inhibitor, with a Ki=315 nM, a σ1 receptor agonist with 5% of its SRI potency, and an α1-adrenoreceptor antagonist with 1–10% of its SRI potency. However, though confirming sertraline's high affinity for σ1 receptors, different studies suggest that the drug actually behaves as an antagonist at those.
Sertraline demonstrated anti-fungal activity against Candida species in vivo. Sertraline also inhibits dynamin 1 dependent endocytosis.
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