The synthesis and biochemical pharmacology of enantiomerically pure methylated oxotremorine derivatives.
Previous pharmacological studies of methylated oxotremorine derivatives bearing substituents at the 3-, 4-, and 5-positions of the pyrrolidinone ring have been conducted using racemic mixtures, and not with optically active compounds. The synthesis and radioligand binding data of optically active, methylated oxotremorine derivatives at the 3- and 4-positions are described. There are significant pharmacological differences between the 3- and 4-position derivatives. The 4-position enantiomers have weak, approximately equal affinity and antagonist-like profiles, whereas the 3-position enantiomers have significantly different affinities and partial agonist-like profiles.
Trybulski
E J
EJ
Medical Research Division of American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965.
Zhang
J
J
Kramss
R H
RH
Mangano
R M
RM
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008297:Male; D008745:Methylation; D019832:N-Methylscopolamine; D010095:Oxotremorine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010890:Pirenzepine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism; D013237:Stereoisomerism
D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D006165:Guanylyl Imidodiphosphate; D010890:Pirenzepine; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate; D019832:N-Methylscopolamine