Conformationally defined adrenergic agents I: potentiation of levarterenol in rat vas deferens by endo- and exo- 2- aminobenzobicyclo[2.2.2]octenes, conformationally defined analogs of amphetamine.
Four conformationally defined analogs of amphetamine were synthesized and studied for their ability to potentiate the action of levarterenol on the isolated vas deferens from reserpine-treated rats. The compunds also were studied for indirect adrenergic agonist activity in the same test system. A definite stereochemical correlation was demonstrated in each case, the exo-isomers being considerably more active than their endo-counterparts both in potentiation and in indirect activity. The more active isomers of each pair correspond to an anti-periplanar conformation of amphetamine. The compounds are probably acting by inhibition of the neuronal amine uptake mechanism, since none of the compounds was a direct-acting agonist itself. These results are discussed in relationship to other previously reported, conformationally defined, amphetamine analogs.
D000588:Amines / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D000588:Amines; D000662:Amphetamines; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D012110:Reserpine; D009638:Norepinephrine