Methylflavonolamine hydrochloride inhibits contractions induced by noradrenaline, calcium and potassium in rabbit isolated aortic strips.
1. The effects of methylflavonolamine hydrochloride (4'-methyl-7-(2-hydroxy-3-isopropylamino-propoxy)-flavone hydrochloride, MFA) were investigated and compared with verapamil and papaverine on rabbit isolated aortic strips, which were contracted by noradrenaline, calcium and potassium. 2. Pre-incubation for 25 min with either MFA (0.03 to 0.2 mM) or papaverine (0.03 to 0.2 mM) induced non-parallel and concentration-dependent rightward displacements of the curves to noradrenaline (0.00001 to 0.1 mM) with the maximal response depressed. The calculated pD2' values (mean +/- s.d.) were 3.89 +/- 0.15 for MFA and 3.93 +/- 0.05 for papaverine, respectively. Verapamil (0.03 to 0.2 mM) inhibited the contraction induced by noradrenaline in a competitive manner with a pA2 value of 5.91 +/- 0.83. 3. In depolarized aortic strips of the rabbit, prior exposure to MFA (0.03 to 0.3 mM) and papaverine (0.03 to 0.2 mM) shifted the cumulative curves to Ca2+ (0.003 to 100 mM) parallel to the right with the maximal responses depressed, pD'2 values being 3.88 +/- 0.05 and 3.89 +/- 0.13, respectively. Verapamil produced comparable inhibition of the contraction at much lower concentrations (30 to 300 nM). 4. MFA (0.03 and 0.1 mM) inhibited the contraction elicited by graded depolarization at a constant Ca2+ concentration with a pD'2 value of 4.09 +/- 0.07. 5. The present results show that MFA has some actions consistent with a calcium antagonist. It resembles papaverine more closely than verapamil.
Zhang
M S
MS
Department of Pharmacology, Shanxi Medical College, Taiyuan, China.
Zhou
E F
EF
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011188:Potassium / Q000037:antagonists & inhibitors*; D011817:Rabbits
D005419:Flavonoids; D044948:Flavonols; D009467:Neuromuscular Depolarizing Agents; C052073:SIPI 549; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine