rand d

MK-196

.. , Saluretic ~Uricosuric Effects Elevated serum urate levels could be a risk faclOr for myocardial infarction. Thus a drug capable of preV~Il{i llg an increase in serum urale might havea useful place in diuretic therapy. The renal pharmacology of M K-196 «6. 7-dichloro-2-mcthyl,!-oxQ.2-phcnyl-5-indanyloxyl acetic acid) as it relates to effects on water, salt and uric acid excretion were !;Iudied in the chimpanzee. This agent is orally active at very low doses and has a prolonged duration of action. Combination experiments with probenecid did nOl show a signiftcantly enhanced or depressed

uricosuric aClivity whether M K- J 96 was given before or after probenecid, respectively. Probenecid-did-not appear to-influence the saluretic and uricosuric activity of M K-196 . Net lubular secretion ofurale was not seen wish MK-I 96: mersalyl­induced net urale secretion was reduced. Changes in urinary pH did not appear to compromise its emcacy, although the uricosuric action may be slightly reduced during alkalosis. On a dose basis , MK-196 was more saluretic and uricosuric than cthacrynic acid or frusemide (furosemide) and had a longer duration of action. However, some increase in potassium excretion occurred aue 10 the marked natriuresis caused by MK-196.

Fand!;' G.M. et ,[. : Jour~1 of PllarmarolosY and Exp(fimCIlI,,1 Tht rapcutics

200: 402 (Feb I ~77)

, , _ Renal Excretion MK-I 96 is a weak organic acid with an excretory pallern similar to that of salicylate and probenecid. In studies in chimpanzees. tubular secretion was round [0 be strongly inhibited by probenecid and high loads of p_aminohippurate. Urinary excre1ion is increased 1 O-rold when the urine is alkaline. The uricosuric activitywaS"Slightly·depressed-by-pyrazinoate· but the diuretic and saluretic effects were not alTected. The interaction of MK·I96 and pyrazinO.lte on urate excretion is in direct contrast to res ults obtained with probenecid and pyraunoale.

f~M!\i, G.M. C\ )1. : Journal of Ptlarmacolosy and F~peT;mcntal TherapcUt;C5 200: 41 J (Feb 1917)

lNPHARMA 19th Marcn. 1917 p8