Molecular modification of anticholinergics as probes for muscarinic receptors. Part 4. Ileal selective muscarinic antagonists.
Systematic studies of the structure-activity relationships of atropine-like anticholinergic drugs have provided valuable information about the nature of the muscarinic receptor. In this study, the pharmacological activities of the (Z) and (E)-isomers of 2-phenylcyclohexyl diethylaminoethyl ether (1 and 2, respectively) in the isolated rat left atrium were investigated and compared with their activities in the isolated rat ileum preparation. Compound 1 was found to be one of the most ileal selective muscarinic antagonists reported to date. Other data concerning possible differences in the receptor-bound conformations of tropate- versus benzilate-derived muscarinic antagonists are also presented.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60612.
M C
MC
Lu
G D
GD
Noble
E B
EB
Thompson
S M
SM
Vogel
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008024:Ligands; D008297:Male; D013058:Mass Spectrometry; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009928:Organ Specificity; D010276:Parasympatholytics / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis
D008024:Ligands; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D002217:Carbachol; D007545:Isoproterenol