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.

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.