α2-Adrenoceptor agonist properties of exo- and endo-isomers of 2-amino-6,7,dihydroxybenzonorbornene designed as rigid catecholamines

Article abstract of DOI:10.1111/j.2042-7158.1983.tb04276.x

A series of N-substituted exo- and endo-isomers of 2-amino-6,7-dihydroxybenzonorbornene, designed as rigid catecholamines, have been studied in the pithed rat in vivo, as vasoconstrictor agents, and as inhibitors of the twitch response in the transmurally stimulated guinea pig ileum. The exo-isomers examined were vasoconstrictor agonists in the pithed rat and inhibited the twitch response of the ileum. The corresponding endo-isomers were inactive in both preparations. The exo-isomers were less potent than the α₂-receptor agonist TL99, but were all directly acting vasoconstrictor agents, since they were still effective in reserpine-pretreated animals. Responses induced by members of the exo-series were selectively antagonized by the α₂-receptor antagonist rauwolscine, but were not antagonized by the α₁-receptor antagonist, prazosin, or the dopamine-receptor antagonist α-flupenthixol. The results demonstrate important conformational requirements for the interaction of catecholamines at presynaptic or postsynaptic α₂-receptors, and suggest that a fully extended or anti-conformation of the noradrenaline molecule is involved in α₂-receptor-agonist interaction.