Nellie E Byun, Michael Grannan, Michael Bubser, Robert L Barry, Analisa Thompson, John Rosanelli, Raajaram Gowrishankar, Nathaniel D Kelm, Stephen Damon, Thomas M Bridges, Bruce J Melancon, James C Tarr, John T Brogan, Malcolm J Avison, Ariel Y Deutch, Jürgen Wess, Michael R Wood, Craig W Lindsley, John C Gore, P Jeffrey Conn, Carrie K Jones
Accumulating evidence suggests that selective M4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M4 activators were unsuccessful because of the lack of M4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M4 positive allosteric modulator (PAM) that exerts central effects after systemic administration. We now report that VU0152100 dose-dependently reverses amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M4 KO mice...
June 2014: Neuropsychopharmacology