Tianeptine metabolite MC5 is an active metabolite of the atypical antidepressant tianeptine.1 It is formed from tianeptine by β-oxidation.2 Tianeptine metabolite MC5 selectively induces G protein activation in bioluminescence resonance energy transfer (BRET) assays using HEK293T cells expressing the human μ-opioid receptor (MOR) over the human δ-opioid receptor (DOR; EC50s = 0.454 and >100 ?M, respectively).1 It decreases immobility in the forced swim test in wild-type mice, but not MOR knockout mice, indicating MOR-dependent antidepressant-like activity when administered at a dose of 30 mg/kg.
References:
[1]. Samuels, B.A., Nautiyal, K.M., Kruegel, A.C., et al.The behavioral effects of the antidepressant tianeptine require the mu-opioid receptorNeuropsychopharmacology42(10)2052-2063(2017).
[2]. Szafarz, M., Wencel, A., Pociecha, K., et al.Pharmacokinetic study of tianeptine and its active metabolite MC5 in rats following different routes of administration using a novel liquid chromatography tandem mass spectrometry analytical methodNaunyn Schmiedebergs Arch. Pharmacol.391(2)185-196(2017).