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.