VU 0255035

VU 0255035 is a M1 muscarinic acetylcholine receptor (mAChR) antagonist (Ki = 14.87 nM). VU 0255035 shows higher selectivity to the M1 orthosteric site than other receptor subtypes. The M(1) mAChR is of particular interest as a potential target for treatment of CNS disorders. Whole-cell patch-clamp recordings demonstrate that VU0255035 inhibits potentiation of N-methyl-D-aspartate receptor currents by the muscarinic agonist carbachol in hippocampal pyramidal cells. VU0255035 has excellent brain penetration in vivo and is efficacious in reducing pilocarpine-induced seizures in mice. VU 0255035 does not induce the severe cognitive deficits seen with nonselective mAChR antagonists and could provide a novel approach for the treatment certain of CNS disorders.

≥98%