Relaxing effect of vesnarinone (OPC-8212) on the tracheal muscle strips isolated from guinea pigs.
The effect of vesnarinone (OPC-8212), an orally active positive inotropic agent was studied in tracheal muscle isolated from guinea pigs, and the mechanism of its action was analyzed. Vesnarinone (10(-6)-10(-4) M) caused a concentration-dependent relaxation of tracheal muscle pre-contracted by 10(-4) M histamine. The potency of the relaxing effect of vesnarinone was greater than that of theophylline; the pD2 values for vesnarinone and theophylline were 4.9 and 4.5, respectively. Vesnarinone reduced the high-K(+)-induced contracture of depolarized tracheal muscle non-competitively (pD'2 = 3.7). Vesnarinone at the low concentration of 3 x 10(-6) M shifted the concentration-response curve for isoproterenol in a parallel fashion to the left. Vesnarinone additively acted on the relaxing effect of isobutyl methyl xanthine. Propranolol (10(-5) M) and reserpine pre-treatment (5 mg/kg, i.p., 24 hr) had no effect on the relaxing effect of vesnarinone. These results suggested that vesnarinone elevated the intracellular cyclic AMP level via phosphodiesterase inhibition, resulting in the tracheal muscle relaxation.
Takeya
K
K
Department of Pharmacology, Aichi Medical University, Japan.
Ando
H
H
Ando
S
S
Yajima
M
M
Nomura
H
H
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone; D006632:Histamine; D012110:Reserpine; D002217:Carbachol; D011433:Propranolol; D007545:Isoproterenol; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine