CHOLINERGIC AGENTS - EFFECT OF METHYL SUBSTITUTION IN A SERIES OF ARECOLINE DERIVATIVES ON BINDING TO MUSCARINIC ACETYLCHOLINE-RECEPTORS

• Published in: Journal of pharmaceutical sciences Vol. 81; no. 10; pp. 1015 - 1019
• Main Authors: MOOS, WH, BERGMEIER, SC, COUGHENOUR, LL, DAVIS, RE, HERSHENSON, FM, KESTER, JA, MCKEE, JS, MARRIOTT, JG, SCHWARZ, RD, TECLE, H, THOMAS, AJ
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.10.1992
• Subjects: Animals; Arecoline - analogs & derivatives; Arecoline - metabolism; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Choline - physiology; Dioxolanes - metabolism; Dioxolanes - pharmacology; Life Sciences & Biomedicine; Muscarinic Antagonists; Parasympathomimetics - metabolism; Parasympathomimetics - pharmacology; Pharmacology & Pharmacy; Physical Sciences; Quinuclidinyl Benzilate - metabolism; Quinuclidinyl Benzilate - pharmacology; Rats; Receptors, Muscarinic - metabolism; Receptors, Muscarinic - physiology; Science & Technology; Structure-Activity Relationship; Tritium; ARECAIDINE; EFFICACY; ANALOGS; AFFINITY; CORTEX; ESTERS; COGNITION ENHANCERS; INFUSIONS; AGONIST BINDING; RAT-BRAIN
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600811012

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.