INHIBITION OF SYMPATHETIC NERVOUS-SYSTEM BY A SERIES OF HETEROCYCLIC CONGENERS OF DOPAMINE

Abstract

A series of heterocyclic congeners of dopamine with different positions of phenolic oxygens and with the possibility of cis and trans isomerism at the 4a-10b ring juncture was evaluated in vitro and in vivo for dopaminergic activity. GJH-166 [trans-4-methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,10b-octa-hydro-benzo-f-quinoline-hydro-bromide] and GJH-171 [cis-4-methyl-7,8-dihydroxy-1,2,3,4,4a,5,6,10b-octa-hydro-benzo-f-quinoline-hydro-bromide], suppressed the positive chronotropic response induced by stimulation of the right cardioaccelerator nerves. These effects were antagonized by haloperidol. GJH-166, in doses as low as 9.5 .times. 10-4 .mu.mol/kg reduced the resting heart rate in cats anesthetized with .alpha.-chloralose. GJH-166 and GJH-171 antagonized pressor responses induced by bilateral carotid occlusion and stimulation of the central stump of the sciatic nerve. The extended conformation of the dihydroxyphenylethylamine moiety of dopamine with a trans isomeric form was favorable for dopaminergic agonist activity.