ICI-206,970 - A NOVEL EUKALEMIC DIURETIC WITH CALCIUM-CHANNEL BLOCKING ACTIVITY

ICI 206,970, an aminomethylphenol pyrazine derivative, produced diuret ic and saluretic effects, but caused only minimal alterations in kalur esis in dogs and rats after oral and parenteral administration. ICI 20 6,970, unlike HCTZ, increased diuretic activity in a more clearly defi ned dose-related manner and did not reach the plateau level even up to a dose of 100 mg/kg p.o. The diuretic and natriuretic response is bel ieved to be a combination of a direct effect on tubule function and ch anges in GFR, particularly at higher doses. Based upon studies in in v itro amphibian models for mimicking mammalian nephron, ICI 206,970 app eared to possess a furosemide-like activity in toad cornea and amilori de-like activity in toad bladder It is concluded that ICI 206,970 is a potent eukalemic diuretic with the potential of multiple sites of ren al action.