PHARMACOLOGICAL ACTIVITIES OF IMIDAZO[1,2-ALPHA]PYRAZINE DERIVATIVES

The smooth relaxant activity and other pharmacological properties of i midazo[1,2-alpha]pyrazine derivatives were compared with those of theo phylline. Imidazol[1,2-alpha]pyrazine derivatives exhibited a potent s mooth muscle relaxant activity regardless of the agent which had elici ted the contraction and thus showed a broad spectrum of non specific s mooth muscle relaxant activity. IN the isolated guinea-pig atria, imid azo[1,2-alpha]pyrazine derivatives exhibited potent inotropic and chro notropic activities. As opposed to theophylline, the imidazo[1,2-alpha ]pyrazine derivatives tested were unable to antagonize the adenosine-i nduced inhibition of spontaneous contractile activity of rabbit ileum. Furthermore, as opposed to theophylline, these derivatives did not ex hibit a marked diuretic activity. Thus it appears that they do not act as adenosine receptor antagonists. Imidazo[1,2-s]pyrazine derivatives inhibited the total cAMP-phosphodiesterase (cGMP-PDE) activities of b ovine trachea but with relatively low potencies, sharing a discrepancy between their activity on isolated tissues and their ability to inhib it PDE. It is suggested that imidazo [1.2-alpha]pyrazine derivatives m ay selectively inhibit type III and/or type IV phosphodiesterase iso-e nzymes involved in the regulation of the mechanical activity of cardia c and smooth muscle tissues.