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

J Cardiovasc Pharmacol. 1993 Jan;21(1):89-94. doi: 10.1097/00005344-199301000-00013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium / pharmacology
  • In Vitro Techniques
  • Indoles / pharmacology*
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Norepinephrine / pharmacology
  • Portal Vein / drug effects
  • Potassium / pharmacology
  • Pyridazines / pharmacology*
  • Rats
  • Rats, Wistar
  • Vasodilator Agents / pharmacology*

Substances

  • Indoles
  • Pyridazines
  • Vasodilator Agents
  • 1-hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino(4,5-b)indole
  • Caffeine
  • Potassium
  • Calcium
  • Norepinephrine