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.
CNS Research, Upjohn Company, Kalamazoo, MI 49001.
V H
VH
Sethy
R F
RF
Heier
M W
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Moon
D000109:Acetylcholine / Q000378:metabolism*; D000114:Acetylene / Q000031:analogs & derivatives; D000588:Amines; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D009116:Muscarine / Q000037:antagonists & inhibitors*; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000588:Amines; D010277:Parasympathomimetics; D010095:Oxotremorine; D009116:Muscarine; D000109:Acetylcholine; D000114:Acetylene