A new antihypertensive compound: 3 hydrazino-6-[(2-hydroxypropyl)methylamino] pyridazine dihydrochloride (ISF 2123)

Abstract

The new 3-hydrazinopyridazine derivative ISF 2123 was demonstrated to posses a potent and long lasting hypotensive action in different animal species both by intravenous and oral route. Data from acute experiments indicate that after i.v. injection the drug produces a clear cut blood pressure drop at dose levels lower than 0,1 mg/kg in anaesthetized cats and conscious hypertensive rats and lower than 0,03 mg/kg in conscious hypertensive dogs. Repeated treatments with oral doses of 1,2,5 mg/kg in hypertensive rats and with 0,1 mg/kg in hypertensive dogs induce a blood pressure fall with no evidence of a cumulative effect or tolerance. After each administration a heart rate increase was observed. In comparative trials ISF 2123 was 4–14 times more potent and 3–10 times less toxic (acute toxicity) than hydralazine. ISF 2123 does not display any specific activity on central nervous system nor in vitro antagonistic effects against acetylcholine, serotonin, histamine, adrenaline and barium chl o ride. Chronic toxicity trials in rats and dogs indicated that doses far higher than those required for hypotensive activity produce no variation of hystological, haematological or haemat o chemical parameters.