Sertraline

Sertraline is a selective serotonin reuptake inhibitor (SSRI) that acts primarily by binding to the serotonin transporter (SERT), inhibiting neuronal reuptake of serotonin and potentiating serotonergic activity in the central nervous system.¹ The therapeutic benefits typically emerge after 4-6 weeks of administration, believed to result from neuroadaptations including downregulation of presynaptic 5-HT1A autoreceptors and downstream increases in brain-derived neurotrophic factor expression.³ Sertraline also displays affinity for sigma-1 receptor binding sites and exhibits relatively high activity as a dopamine transporter inhibitor, occupying approximately 20% of DAT receptors at doses of 200mg and above, though the clinical relevance of these secondary actions remains uncertain. The drug shows weak inhibitory effects on norepinephrine reuptake and has been observed to increase extracellular dopamine in the nucleus accumbens and striatum at clinically relevant doses in animal studies.⁴ Sertraline exhibits little to no affinity for GABA, histamine, acetylcholine, benzodiazepine, or serotonergic receptors (5-HT1A, 5-HT1B, 5-HT2), and does not exert significant anticholinergic, antihistamine, or adrenergic blocking activity.¹