Adrenoceptor and tetrabenazine antagonism activities of some pyridinyltetrahydropyridines.
A series of pyridinyltetrahydropyridine derivatives was synthesized and evaluated as adrenoceptor and tetrabenazine antagonists. 4-(3-Fluoro-2-pyridinyl)-1,2,5,6-tetrahydropyridine proved to be the most potent and selective alpha 2-adrenoceptor antagonist of the series as measured in vitro by displacement of [3H]clonidine and [3H]prazosin from membrane binding sites of calf cerebral cortex and by antagonism of the effects of clonidine and methoxamine in the rat isolated, field-stimulated vas deferens. In addition, this compound, and the corresponding desfluoro derivative, blocked tetrabenazine-induced ptosis in the mouse.
D000818:Animals; D001763:Blepharoptosis / Q000188:drug therapy; D002540:Cerebral Cortex / Q000378:metabolism; D003000:Clonidine / Q000037:antagonists & inhibitors; D008297:Male; D008729:Methoxamine / Q000037:antagonists & inhibitors; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013747:Tetrabenazine / Q000037:antagonists & inhibitors*
D011725:Pyridines; D011942:Receptors, Adrenergic, alpha; D008729:Methoxamine; D003000:Clonidine; D013747:Tetrabenazine