An alpha-adrenoceptor inhibitory action of kynuramine

Kynuramine, an endogenously occurring amine, inhibited the vasoconstrictor responses to norepinephrine in the isolated perfused mesenteric arteries of rats and blocked the relaxation of rabbit intestinal smooth muscle by phenylephrine. Similarly, kynuramine reversed clonidine-induced inhibition of the cholinergic twitch response in the guinea pig ileum. These effects, seen with concentration ranging from 4 to 60 microgram/ml, are consistent with an alpha-adrenoceptor inhibitory action of kynuramine at both presynaptic and postsynaptic sites. Kynuramine itself, lacked intrinsic activity on alpha-adrenoceptors and showed a complete lack of affinity for beta-adrenoceptors in the rabbit intestine and guinea pig tracheal chain preparation. None of the effects of kynuramine could be attributed to the formation of 4-hydroxyquinoline, the deaminated metabolite of kynuramine. Additionally, no evidence was obtained for an action on muscarinic receptors or non-specific effects on vascular smooth muscle. However, a slight, transient stimulant action was evident on intestinal smooth muscle. It is concluded that kynuramine inhibits both presynaptic and postsynaptic alpha-adrenoceptors in vitro and it is conceivable that the compound might function as an endogenous inhibitor of alpha-adrenoceptors in vivo.