MRK-016 is a selective GABAA α5 receptor inverse agonist/ negative allosteric modulator, (IC50=3 nM) with the advantages of being orally available and penetrating the blood-brain barrier.MRK-016 increases long time period potentiation (LTP) in mouse hippocampal slices, with memory-improvement, antidepressant, and pain-treating effects.

GABAA α3β3γ2 (human):0.77 nM (Ki), GABAA α1β3γ2 (human):0.83 nM (Ki), GABAA α2β3γ2 (human):0.85 nM (Ki), GABAA α5β3γ2 (human):1.4 nM (Ki), GABAA α5:3 nM (EC50)

MRK-016 is a selective, orally bioavailable inverse GABAA α5 receptor agonist(EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77?and 1.4?nM for human?GABAA?α1β3γ2, GABAA?α2β3γ2, GABAA?α3β3γ2, and GABAA?α5β3γ2, respectively)[1].

MRK-016 (0.3, 1, or 3 mg/kg p.o.) shows cognition-enhancing activity in the delayed matching-to-position version of the Morris water maze. MRK-016 (1, 3, or 10 mg/kg i.p.) does not produce kindling in mice[2]. MRK-016 (3 mg/kg, i.p.) protects against LPS-induced learning/memory decrements in mice[3].