Vasorelaxant action of caroverine fumarate (a quinoxaline derivative), a calcium-blocking agent.

1 Caroverine fumarate, 1-(2-diethylaminoethyl)-3-(p-methoxy-benzyl)-1,2-dihydro-2-quinoxalinone fumarate, caused a greater inhibition of the pressor response to KCl (8 x 10(-2) M) than that to noradrenaline (10(-6) M) in the rat hindquarter preparation. 2 In the isolated aorta of the rat, caroverine (up to 10(-6) M) markedly suppressed the contraction caused by KCl (4 x 10(-2) M) (high-K) but had little effect on the contractile response to noradrenaline (10(-6) M) whether added before the spasmogen or in its presence. 3 In the high-K-treated aorta, caroverine shifted the concentration-response curve for external calcium to the right, competitively. The negative logarithm of the affinity (pA2) of caroverine was calculated to be approx. 7. 4 Increased 45Ca uptake of the high-K-treated aorta measured by a modified lanthanum method was inhibited by either caroverine (3 x 10(-6) M) or verapamil (10(-6) M). 5 Concentrations of caroverine and verapamil reducing high-K-induced aortic contraction to 50% of its maximum were 2.4 x 10(-7) and 6.6 x 10(-8) M respectively. 6 Following washout the caroverine-induced inhibition of high-K-induced aortic contraction was more rapidly restored than the verapamil-induced inhibition. 7 These results suggest that caroverine fumarate is a specific and readily reversible calcium influx inhibitor in the rat vascular smooth muscle.