Effects of tertatolol on post- and prejunctional beta adrenoceptors.
The effects of tertatolol, a new and powerful beta adrenoceptor blocking drug, on post- and prejunctional beta receptors were investigated; canine vascular tissues (saphenous veins, coronary arteries and splenic arteries) and guinea-pig trachea and atria were used. At concentrations below 10(-5) M, tertatolol did not alter basal tension or contractile responses to electrical stimulation, norepinephrine, K+ or prostaglandin F2 alpha; at doses at or above 10(-5) M the drug-evoked contractions which were reduced by phentolamine and were absent in denervated veins. Tertatolol at 10(-5) M and 3 X 10(-5) M augmented the basal efflux of [3H] norepinephrine in saphenous veins labeled with the 3H-transmitter. In veins, 10(-5) M of tertatolol depressed the contractions caused by electrical stimulation without affecting those to exogenous norepinephrine; this concentration of the drug also inhibited the stimulation-induced overflow of [3H]norepinephrine. The major part of the present study was designed to test the beta receptor blocking properties of tertatolol and to compare its effects with those of propranolol. Tertatolol inhibited, in a concentration-dependent manner, the relaxations caused by isoproterenol in saphenous veins, splenic arteries and coronary arteries and the relaxations evoked by norepinephrine and epinephrine in coronary arteries; the potency of tertatolol was higher than that of propranolol. In trachea and right atria of the guinea-pig, tertatolol inhibited, in a concentration-dependent manner, the dose-response curves to isoproterenol; the relative potency of tertatolol was higher than that of propranolol. In dog saphenous veins, previously incubated with [3H]norepinephrine, tertatolol (10(-7)M) blocked the increased stimulation-evoked overflow of the 3H-transmitter induced by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)
Verbeuren
T J
TJ
Laekeman
G
G
Majchrowicz
B B
BB
Jordaens
F H
FH
Zonnekeyn
L L
LL
Herman
A G
AG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D015237:Dinoprost; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013876:Thiophenes; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011460:Prostaglandins F; D011943:Receptors, Adrenergic, beta; D013876:Thiophenes; D008734:Methoxyhydroxyphenylglycol; C005632:tertatolol; D015237:Dinoprost; D007545:Isoproterenol; D011188:Potassium; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D004837:Epinephrine