GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR[3]. MK-0343 binds to α1-, α2-, α3- and α5-containing human recombinant GABAA receptors with comparable high affinity (0.21-0.40 nM)[4]. This compound readily penetrates the brain in rats and occupies the benzodiazepine site of GABAA receptors, with an Occ50 of 2.2 mg/kg p.o. and a corresponding plasma EC50 of 115 ng/mL[4]. MK-0343 causes sedation in humans at a dose of 2 mg, corresponding to levels of occupancy considerably less than those predicted from rodent models to be required for anxiolytic efficacy (∼35-65%)[4]. MK-0343 0.75 mg was equipotent with lorazepam as indicated by saccadic peak velocity (SPV) (-42.4 deg/s), saccadic latency (0.02 s) and Visual Analogue scales (VAS) alertness scores (1.50 ln mm), while effects on memory and postural stability were smaller[5].
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