alpha-Methyl analogues of acetylenic amines as striatal muscarinic antagonists

J Pharm Pharmacol. 1991 Sep;43(9):670-1. doi: 10.1111/j.2042-7158.1991.tb03562.x.

Abstract

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.

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylene / analogs & derivatives
  • Amines
  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Injections, Intraperitoneal
  • Muscarine / antagonists & inhibitors*
  • Oxotremorine / analogs & derivatives
  • Oxotremorine / pharmacology*
  • Parasympathomimetics / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Amines
  • Parasympathomimetics
  • Oxotremorine
  • Muscarine
  • Acetylcholine
  • Acetylene