RT Journal Article
SR Electronic
T1 POTENTIATION OF DIURETIC EFFECTS OF METHYL XANTHINES AND PYRIMIDINES BY CARBONIC ANHYDRASE INHIBITORS
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 276
OP 283
VO 144
IS 2
A1 Bohdan H. Nechay
YR 1964
UL http://jpet.aspetjournals.org/content/144/2/276.abstract
AB Administration of theophylline, caffeine, aminoisometridine or aminometridine to dogs caused a urinary electrolyte excretion pattern which was characterized by quantitative pre-dominance of Na+ and Cl- with smaller amounts of K+ and virtually no HCO3- in acid urine. Following simultaneous intravenous injection of any of these with acetazolamide, Cl-, HCO3- and Na+ excretion rates were increased greatly above the sum of separate effects of each agent, but the effects on K+ output were generally additive. Theophylline was also potentiated by other general carbonic anhydrase inhibitors, methazolamide and ethoxzolamide. At one dose combination of acetazolamide and theophylline there was a consistent drop in inulin clearance averaging 13%. Glomerular filtration rate was not measured at other doses or with other drugs. Theophylline was not potentiated by CL 13,850, an analogue of acetazolamide which is devoid of carbonic anhydra. se inhibitory activity. Another analogue, CL 11,366, which at doses studied is an inhibitor of renal but not erythrocytic carbonic anhydrase (nor presumably that of other sites), gave results similar to theophylline-acetazolamide combination indicating renal site of potentiation. Potentiation effects observed were considered to be a function of increased intracellular pH of renal tubules due to carbonic anhydrase inhibition favoring the activity of methyl xanthines and pyrimidines. The Williams & Wilkins Company