title: Pharmacological characterization of the vasodilator effect of DF-100, a new pyridazino[4,5-b]indole, in vascular smooth muscle.
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.
authors.affiliation: Pharmacology Department, Universidad de Navarra, Pamplona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Frechilla
authors.forename: E
authors.initials: E
authors.lastname: Castiella
authors.forename: B
authors.initials: B
authors.lastname: Lasheras
authors.forename: E
authors.initials: E
authors.lastname: Cenarruzabeitia
authors.forename: A
authors.initials: A
authors.lastname: Monge
authors.forename: I
authors.initials: I
authors.lastname: Aldana
authors.forename: T
authors.initials: T
authors.lastname: Alvarez
authors.forename: M J
authors.initials: MJ
authors.lastname: Losa
authors.forename: M
authors.initials: M
authors.lastname: Font
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D007211:Indoles; D011724:Pyridazines; D014665:Vasodilator Agents; C071273:1-hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino(4,5-b)indole; D002110:Caffeine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine