RESEARCH MONOGRAPH · KDC-MN-202
Sertraline
Sertraline (Zoloft) is one of the most widely prescribed psychiatric medications on the planet. Pfizer brought it to market in 1991 as a follow-on to Prozac with a slightly different shape and a slightly different side-effect profile. The main action is the standard SSRI move: block serotonin from being recycled back into the cell that fired it. A small bonus is mild blockade of the dopamine pump, which a few researchers credit with the somewhat brighter subjective profile some patients report compared to other SSRIs. Approved for depression, OCD, panic, PTSD, social anxiety, and premenstrual mood disorder. Generally considered first-line and reasonably well tolerated. Not stocked by Kodiac. This monograph is provided for research and educational reference.
Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.
Selective serotonin reuptake inhibitor
A naphthylamine SSRI with mild dopamine reuptake inhibition; one of the most prescribed psychiatric medications worldwide.
Abstract
Sertraline ((1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine; CAS 79617-96-2; molecular formula C17H17Cl2N; molecular weight 306.23) is a tetrahydronaphthalene SSRI synthesized at Pfizer in 1977 and approved by the FDA in 1991 under the trade name Zoloft. SERT affinity is nanomolar (Ki approximately 0.3 nM); the compound exhibits weak dopamine transporter inhibition (Ki approximately 25 nM) that is unusual within the SSRI class and may contribute to a subtly different subjective profile. Plasma half-life is 22 to 36 hours; the principal metabolite N-desmethylsertraline is pharmacologically active but with reduced SERT affinity. Hepatic metabolism is via CYP2B6, CYP2C19, CYP2D6, and CYP3A4; clinically relevant CYP2D6 inhibition exists but is weaker than fluoxetine or paroxetine. Approved indications include major depressive disorder, OCD, panic disorder, PTSD, social anxiety disorder, and premenstrual dysphoric disorder. Used as a reference compound in SERT binding studies and animal models of depression and anxiety; the dichlorophenyl moiety is a target structural feature in numerous SSRI structure-activity relationship studies.
Mechanism of action
High-affinity SERT inhibition with weak DAT inhibition. Active metabolite N-desmethylsertraline is pharmacologically present but less potent.
Reported research dose ranges
Reported research dose ranges in the literature.
References
- Koe BK, et al. Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin. J Pharmacol Exp Ther 1983.
- DeVane CL, Liston HL, Markowitz JS. Clinical pharmacokinetics of sertraline. Clin Pharmacokinet 2002.
- Murdoch D, McTavish D. Sertraline. A review. Drugs 1992.
Read the full monograph
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The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.
FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.