Pharmacological profile of the 2-alkynyladenosine derivative 2-octynyladenosine (YT-146) in the cardiovascular system.
We investigated the cardiovascular effects of 2-octynyladenosine (YT-146), an adenosine A2 agonist, in various mammalian preparations in comparison with adenosine and 2-chloroadenosine. YT-146, when intravenously administered, caused a dose-dependent decrease of blood pressure in anesthetized normotensive rats (with ED30 values of 0.4 micrograms/kg), and YT-146 was 250 times more potent than adenosine. Whereas adenosine and 2-chloroadenosine decreased heart rate at approximately equihypotensive doses, YT-146 had no negative chronotropic effects at h hypotensive doses. Orally given YT-146 (0.1 - 1 mg/kg) produced a potent and long-lasting antihypertensive effect in spontaneously hypertensive rats. YT-146 was 15.9 and 12.5 times more potent than adenosine in producing relaxation of isolated porcine coronary arteries and in increasing dog coronary blood flow, respectively. Although YT-146 was equipotent to adenosine in causing a negative inotropic effect in isolated guinea pig atria, it was less potent than adenosine in producing atrioventricular conduction block in guinea pigs. On the other hand, 2-chloroadenosine was 9.1, 1.8 and 2.4 times more potent than adenosine in lowering blood pressure, relaxing isolated porcine coronary arteries and increasing dog coronary blood flow, respectively. 2-Chloroadenosine was the most potent in producing cardiodepression, i.e., negative inotropy and atrioventricular conduction block in guinea pigs. From these results, we concluded that YT-146 is a potent coronary vasodilator and also a potent, orally active and long-acting hypotensive agent having less cardiac depressant activity.
Kogi
K
K
R & D Department, Toa Eiyo, Ltd., Fukushima, Japan.
Uchibori
T
T
Aihara
K
K
Yamaguchi
T
T
Abiru
T
T
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D016275:Atrial Function; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D003864:Depression, Chemical; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006325:Heart Atria / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D000480:Alkynes; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D011189:Potassium Chloride; C070494:YT 146; D000241:Adenosine