Tianeptine-d6 (hydrochloride)

Tianeptine-d₆ is intended for use as an internal standard for the quantification of tianeptine by GC- or LC-MS. Tianeptine is an atypical antidepressant.¹ It is an agonist of the μ-opioid receptor (MOR; EC₅₀s = 194 and 641 nM for human and mouse receptors, respectively, in a BRET assay for G protein activation) and also has effects on the glutamate system.^1,2 Tianeptine (30 mg/kg) decreases immobility in the forced swim test in wild-type, but not MOR knockout mice, indicating antidepressant-like activity dependent on MORs.³ It increases locomotor activity at a dose of 30, but not 10 mg/kg, in the open field test and increases paw withdrawal latency in the hot-plate test in mice. Tianeptine modulates AMPA receptor activity by increasing phosphorylation of the AMPA receptor GluR1 subunit in the frontal cortex and hippocampal CA3 region in mice.⁴ It prevents increases in glial glutamate transporter 1 (GLT-1) expression induced by chronic restraint stress in the hippocampal CA3 region in rats when administered at a dose of 10 mg/kg per day for 21 days.⁵ It also reverses increases in extracellular glutamate levels induced by acute restraint stress in the basolateral nucleus of the amygdala in rats.⁶

1.McEwen, B.S., Chattarji, S., Diamond, D.M., et al.The neurobiological properties of tianeptine (Stablon): From monoamine hypothesis to glutamatergic modulationMol. Psychiatry15(3)237-249(2010) 2.Gassaway, M.M., Rives, M.L., Kruegel, A.C., et al.The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonistTransl. Psychiatry4e411(2014) 3.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) 4.Svenningsson, P., Bateup, H., Qi, H., et al.Involvement of AMPA receptor phosphorylation in antidepressant actions with special reference to tianeptineEur. J. Neurosci.26(12)3509-3517(2007) 5.Reagan, L.P., Rossell, D.R., Wood, G.E., et al.Chronic restraint stress up-regulates GLT-1 mRNA and protein expression in the rat hippocampus: Reversal by tianeptineProc. Natl. Acad. Sci. USA101(7)2179-2184(2004) 6.Reznikov, L.R., Grillo, C.A., Piroli, G.G., et al.Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: Differential effects of antidepressant treatmentEur. J. Neurosci.25(10)3109-3114(2007)