Vortioxetine
Vortioxetine. Multimodal agent: SERT inhibition plus direct receptor-level modulation (5-HT3 + 5-HT7 + 5-HT1D antagonism, 5-HT1A full agonism… Oral half-life 2.4 d.
Multimodal agent: SERT inhibition plus direct receptor-level modulation (5-HT3 + 5-HT7 + 5-HT1D antagonism, 5-HT1A full agonism, 5-HT1B partial agonism). The additional receptor actions are proposed to explain the cognitive-performance signal (processing speed, executive function) seen in some MDD trials and the lower GI side-effect burden vs classical SSRIs. Not an abrupt-withdrawal agent — long t½ smooths discontinuation.
PK: THE CLEANEST RECORD IN THIS BATCH, AND MY PRIOR ABOUT IT WAS WRONG. I flagged its half-life as "long (~66 h)"; the record stores 57 and its citation says 57 verbatim — "a mean elimination half-life of 57 hr" — while 66 h is the REVIEW value and 65.8 h the population estimate. All three are defensible and the stored one matches its own source exactly. F 0.75 is likewise verbatim, "The absolute bioavailability was 75%", from an intravenous-plus-oral study in 97 volunteers. NO CHANGE. Two values remain unsourced and are declared: V 2600 L appears in no abstract, and the one published figure, 1.97e3 L, is a CENTRAL compartment volume rather than a one-compartment analogue, so swapping it in would be worse; ka 0.5 is uncited but is NOT a back-derivation, implying a 7.6 h peak that sits inside the observed late-Tmax window rather than on a round number. The analyte question closes cleanly: "The major metabolite is pharmacologically inactive".
Pharmacokinetics
- Oral — t½ 2.4 d · F 75% · ka 0.559 h⁻¹ · Vd 2600 L
Sources: PMID:29189941, PMID:23428337, PMID:21486038, PMID:22448783