ICI 206,970: a novel eukalemic diuretic with calcium channel blocking activity.
ICI 206,970, an aminomethylphenol pyrazine derivative, produced diuretic and saluretic effects, but caused only minimal alterations in kaliuresis in dogs and rats after oral and parenteral administration. ICI 206,970, unlike HCTZ, increased diuretic activity in a more clearly defined 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 believed to be a combination of a direct effect on tubule function and changes in GFR, particularly at higher doses. Based upon studies in in vitro amphibian models for mimicking mammalian nephron, ICI 206,970 appeared to possess a furosemide-like activity in toad cornea and amiloride-like activity in toad bladder. It is concluded that ICI 206,970 is a potent eukalemic diuretic with the potential of multiple sites of renal action.
Kau
S
S
Department of Pharmacology and Chemistry, ICI Americas Inc., Wilmington, DE.
Johnston
P
P
Li
J
J
Zuzack
J
J
Leszczynska
K
K
Yochim
C
C
Schwartz
J
J
Giles
R
R
D000818:Animals; D002024:Bufo marinus; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004573:Electrolytes / Q000652:urine; D005260:Female; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007677:Kidney Function Tests; D008297:Male; D011188:Potassium / Q000097:blood*; D011719:Pyrazines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D001743:Urinary Bladder / Q000187:drug effects
D002121:Calcium Channel Blockers; D004232:Diuretics; D004573:Electrolytes; D011719:Pyrazines; D006852:Hydrochlorothiazide; C079771:ICI 206970; D011188:Potassium; D007213:Indomethacin