alpha-Methyl analogues of acetylenic amines as striatal muscarinic antagonists

The effect of acetylenic amines, with or without alpha-methyl substitution, on striatal acetylcholine (ACh) concentration in rats was investigated. Oxotremorine, oxotremorine-1, and U-77053 (trimethyl (4-(1-pyrrolidinyl)-2 butynyl)-urea), the unsubstituted amines, increased striatal ACh concentration. On the other hand, the corresponding alpha-methyl substituted analogues, alpha-methyl-oxotremorine, BM-5, and alpha-methyl U-77053, decreased the concentration of ACh in the striatum. The results indicate that substitution of alpha-methyl in acetylenic amines converts compounds from agonists to antagonists for striatal muscarinic receptors.