Vasomolol: an ultra short-acting and vasorelaxant vanilloid type beta 1-adrenoceptor antagonist.
The ultra-short-acting and vasorelaxant beta 1-adrenoceptor blocking activities of vasomolol, a guaiacoxypropanolamine derivative of vanillic acid ethyl ester, were studied. Vasomolol (0.5, 1.0, 3.0 mg/kg intravenously, i.v.) produced a dose-dependent bradycardia response and demonstrated particularly a hypotensive action with an ultra-short-acting property in pentobarbital-anesthetized normotensive rats. Vasomolol's steady state of beta-blockade was attained < or = 10 min after initial infusion, and a rapid recovery from blockade occurred after discontinuation of the infusion, although intravenous infusion of vasomolol (300 micrograms/kg/min) could not inhibit pressor responses induced by (-)phenylephrine (10 micrograms/kg i.v.). In isolated rat thoracic aorta, vasomolol (1-10 microM) inhibited vascular smooth muscle contractions induced by both (-)phenylephrine (10(-5) M) and high K+ (75 mM) concentration dependently. This inhibitory effect of vasomolol was more sensitive on K(+)-induced than on (-)phenylephrine-induced contractions, suggesting that the block of Ca2+ influx may involve the major mechanism of vasorelaxation. In isolated guinea pig tissues, vasomolol (0.01-10 microM) antagonized the (-)isoproterenol (ISO)-induced positive inotropic and chronotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)ISO suggested that vasomolol was a beta-adrenoceptor competitive antagonist. The effect of vasomolol was more potent on atria than on tracheal tissues, indicating that it possesses beta 1-adrenoceptor selectivity. In addition, vasomolol did not show intrinsic sympathomimetic activity (ISA). Moreover, the binding characteristics of vasomolol were evaluated in [3H]dihydroalprenolol ([3H]DHA) binding to porcine ventricular membranes. Vasomolol was an ultra-short-acting and highly selective beta 1-adrenoceptor antagonist with vasorelaxant activity and is devoid of ISA.
Lin
Y T
YT
Department of Cardiovascular Surgery, Kaohsiung Medical College, Taiwan, R.O.C.
Wu
B N
BN
Wu
J R
JR
Lo
Y C
YC
Chen
L C
LC
Chen
I J
IJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D003864:Depression, Chemical; D004082:Dihydroalprenolol / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; C101861:vasomolol; D004082:Dihydroalprenolol; D014641:Vanillic Acid; C036604:esmolol