MK-0343, also known as MRK-409, is a GABAA receptor subtype-selective partial agonist that exhibits non-sedating anxiolytic activity in preclinical species but induces sedation in humans, binding with high affinity to α1-, α2-, α3-, and α5-containing human recombinant GABA(A) receptors while demonstrating greater agonist efficacy at α3 relative to α1 subtypes, thereby providing mechanistic insight into subtype-specific modulation of inhibitory neurotransmission.

GABAA α2 receptor:0.4 nM (Ki), GABAA α1  receptor:0.22 nM (Ki)

MK-0343 exhibits affinity for recombinant rat GABAA receptors containing α 1, α 2, α 3, and α 5 subunits, with Ki values of 0.22 nM, 0.4 nM, 0.21 nM, and 0.23 nM, respectively [1].

In male Sprague-Dawley rats, oral administration of MK-0343 results in brain penetration and the occupation of benzodiazepine binding sites on GABAA receptors. The dose required to achieve 50% receptor occupancy (Occ50) is 2.2 mg/kg (p.o.), which corresponds to a plasma concentration (EC50) of 115 ng/mL. Preclinical models using these animals indicate that the compound behaves as an anxiolytic without inducing significant sedation at concentrations sufficient for receptor modulation [1].

DMSO: 200 mg/mL (503.3 mM), Sonication is recommended.