Pharmacological characterization of the vasodilator effect of DF-100, a new pyridazino[4,5-b]indole, in vascular smooth muscle.

DF-100, i.e., 1-hydrazino-4-(3,5-dimethyl-1-pyrazolyl)-5H-pyridazino[4,5-b ]indole is a new pyridazino[4,5-b]indole derivative related to dihydralazine. The inhibitory effects of DF-100 were investigated on the contractions in isolated aorta and portal vein. In rat aorta, DF-100 inhibited both K(+)-induced as well as norepinephrine-induced contractions. DF-100 also caused dose-dependent relaxation of contractions produced by 80 mM K+. Moreover, DF-100 significantly inhibited the CaCl2 dose response in high-K+ depolarizing medium. DF-100 inhibited the phasic contractile response to norepinephrine and the caffeine-induced response, suggesting that this molecule affects the mobilization of Ca2+ from a membrane-bound pool. In rat portal vein, DF-100 inhibited the spontaneous rhythmic contractions. The results obtained in this study in isolated rat aorta and portal vein suggest that DF-100 has a direct vasodilating effect that could be attributed to inhibition of cellular Ca2+ influx and release from intracellular stores.