Cholinergic agents: effect of methyl substitution in a series of arecoline derivatives on binding to muscarinic acetylcholine receptors.
Arecoline, arecaidine, and a series of derivatives, differing by the presence or absence of methyl groups at positions on the periphery of the molecule, were prepared, and their binding to muscarinic acetylcholine receptors was tested. On the basis of this study, muscarinic agonism for arecoline series is governed by strict structure-activity relationships, as previously observed for other agonist series. Only minor changes in nitrogen substitution were tolerated in the present series of arecoline derivatives.
Moos
W H
WH
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48106-1047.
Bergmeier
S C
SC
Coughenour
L L
LL
Davis
R E
RE
Hershenson
F M
FM
Kester
J A
JA
McKee
J S
JS
Marriott
J G
JG
Schwarz
R D
RD
Tecle
H
H
D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives* / Q000378:metabolism; D002794:Choline / Q000502:physiology*; D004148:Dioxolanes / Q000378:metabolism / Q000494:pharmacology; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics / Q000378:metabolism / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism* / Q000502:physiology; D013329:Structure-Activity Relationship; D014316:Tritium
D004148:Dioxolanes; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; C015688:arecaidine; D014316:Tritium; C024310:2-methyldioxolane; D001115:Arecoline; D011813:Quinuclidinyl Benzilate; D002794:Choline