title: Synthesis of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives and their evaluation as muscarinic receptor ligands.
abstract: A series of 1-methyl-5-(pyrazol-3- and -5-yl- and 1, 2, 4-triazol-3- and 5-yl)-1, 2, 3, 6-tetrahydropyridine derivatives structurally related to arecoline were synthesized and evaluated on M(1), M(2), and M(3) muscarinic receptors using [(3)H] pirenzepine and [(3)H] NMS as ligands. The binding affinity depended on the position and size of the substituents. The most interesting compounds were further evaluated in functional studies on isolated organs and in vivo for cholinergic side effects. Compounds 5 l and 6 i good M(1) and M(3) antagonistic properties in vitro and were devoid of cholinergic side effects in vivo.
authors.affiliation: Laboratorio di Chimica del Far maco, Istituto Superiore di Sanità, Rome, Italy. mr.delgiudice@iss.it
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Del Giudice
authors.forename: Carlo
authors.initials: C
authors.lastname: Mustazza
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.forename: Franco
authors.initials: F
authors.lastname: Gatta
authors.forename: Khosrow
authors.initials: K
authors.lastname: Tayebati
authors.forename: Francesco
authors.initials: F
authors.lastname: Amenta
authors.forename: Paolo
authors.initials: P
authors.lastname: Tucci
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieretti
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive; D018678:Cholinergic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009928:Organ Specificity; D010095:Oxotremorine / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013552:Swine; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D018678:Cholinergic Agents; D008024:Ligands; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011720:Pyrazoles; D011725:Pyridines; D011976:Receptors, Muscarinic; D014230:Triazoles; D010095:Oxotremorine; D001285:Atropine