Pharmacological activities of imidazo[1,2-alpha]pyrazine derivatives.
The smooth muscle relaxant activity and other pharmacological properties of imidazo[1,2-alpha]pyrazine derivatives were compared with those of theophylline. Imidazo[1,2-alpha]pyrazine derivatives exhibited a potent smooth muscle relaxant activity regardless of the agent which had elicited the contraction and thus showed a broad spectrum of non specific smooth muscle relaxant activity. In the isolated guinea-pig atria, imidazo[1,2-alpha]pyrazine derivatives exhibited potent inotropic and chronotropic activities. As opposed to theophylline, the imidazo[1,2-alpha]pyrazine derivatives tested were unable to antagonize the adenosine-induced inhibition of spontaneous contractile activity of rabbit ileum. Furthermore, as opposed to theophylline, these derivatives did not exhibit a marked diuretic activity. Thus it appears that they do not act as adenosine receptor antagonists. Imidazo[1,2-alpha]pyrazine derivatives inhibited the total cAMP-phosphodiesterase (cAMP-PDE) and the total cGMP-phosphodiesterase (cGMP-PDE) activities of bovine trachea but with relatively low potencies, sharing a discrepancy between their activity on isolated tissues and their ability to inhibit PDE. It is suggested that imidazo[1,2-alpha]pyrazine derivatives may selectively inhibit type III and/or type IV phosphodiesterase isoenzymes involved in the regulation of the mechanical activity of cardiac and smooth muscle tissues.
Michel
A
A
Laboratoire de Pharmacodynamie, CNRS (Centre National de la Recherche Scientifique), Faculté de Pharmacie, Montpellier, France.
Laurent
F
F
Chapat
J P
JP
Boucard
M
M
Bonnet
P A
PA
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002417:Cattle; D004231:Diuresis / Q000187:drug effects; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D002317:Cardiovascular Agents; D007093:Imidazoles; D010276:Parasympatholytics; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D013806:Theophylline; D000241:Adenosine; D002118:Calcium