Hexocyclium derivatives with a high selectivity for smooth muscle muscarinic receptors.
1. The affinity of a number of derivatives of the muscarinic antagonist, hexocyclium, containing an amidine cationic head, for guinea-pig cardiac and ileal receptors was investigated. 2. All the compounds studied displayed a greater affinity for muscular than for cardiac muscarinic receptors. 3. The 5 fold ileal selectivity of hexocyclium was increased by a number of chemical substitutions. The largest discrimination between receptors (about 200 fold) was found for the formamidine derivative. 4. The selectivity displayed by the hexocyclium derivatives stemmed from a greater decrease in affinity towards cardiac as compared to ileal receptors.
Micheletti
R
R
Department of Pharmacology, Istituto De Angeli, Milano, Italy.
Schiavone
A
A
Cereda
E
E
Donetti
A
A
D000818:Animals; D001626:Bethanechol Compounds / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D005559:Formamides / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism* / Q000494:pharmacology; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D001626:Bethanechol Compounds; D005559:Formamides; D010276:Parasympatholytics; D010879:Piperazines; D011976:Receptors, Muscarinic; C015922:hexocyclium