Conformational analogues of dopamine. Synthesis and pharmacological activity of (E)- and (Z)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides.
(E)- and (Z)-(+/-)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides were synthesized as part of a program to assess the importance of conformational isomerism with respect to the various peripheral biological actions of dopamine. Although neither of the compounds possessed dopaminergic activity in the canine renal blood-flow model, both agents were weak alpha-adrenergic agonists and exhibited cardiostimulatory properties similar to dopamine. The E isomer was apprxoximately 5 times more potent than the Z isomer in its alpha-adrenergic activity and approximately 15 times as potent in its cardiac effects. Possible reasons for the lack of renal dopaminergic activity exhibited by the E isomer are presented.
D000316:Adrenergic alpha-Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003521:Cyclopropanes; D004285:Dogs; D004298:Dopamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D008297:Male; D008968:Molecular Conformation; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits; D013237:Stereoisomerism; D014665:Vasodilator Agents
D000316:Adrenergic alpha-Agonists; D003521:Cyclopropanes; D014665:Vasodilator Agents; D004298:Dopamine