Enhancement of uricosuric properties of indacrinone by manipulation of the enantiomer ratio.

Racemic indacrinone is a high-ceiling, relatively long-acting diuretic. Both enantiomers have uricosuric activity, but the diuretic activity resides predominantly in the (-) enantiomer. Usual therapeutic doses of racemic indacrinone have only transient uricosuric activity, so that, as with other diuretics, hyperuricemia occurs. Sixty-five healthy men participated in a multicenter, double-blind, randomized, balanced, incomplete-block study comparing the effects on plasma urate and urate clearance of indacrinone (-) enantiomer 10 mg given concomitantly with 0, 10, 20, 40, and 80 mg (+) enantiomer (10/0, 10/10, 10/20, 10/40, 10/80), as single daily doses for 7 days. Hydrochlorothiazide (HCTZ) 50 mg daily and ticrynafen (T) 250 mg daily were controls. Each subject received two of the seven treatments, so that there were 18 subjects per treatment. On days 7 to 8, morning (mean of 0-hr values on days 7 and 8), HCTZ, 10/0, 10/10, and 10/20 elevated plasma urate by 8% to 16%. 10/40 was approximately isouricemic, and 10/80 and T lowered plasma urate by 13% and 41%. There were corresponding changes in urate clearance.

A double-blind comparison of a novel indanone diuretic (MK-196) with hydrochlorothiazide in the treatment of essential hypertension.

1 The antihypertensive effect and tolerability of MK-196 (10 mg and 15 mg daily) was compared to hydrochlorothiazide (HCT; 50 mg daily) in a 4-week multiclinic, double-blind study involving 42 patients with mild to moderate, essential hypertension. 2 Both doses of MK-196 were as effective and sometimes more effective than HCT in lowering standing and supine systolic and diastolic blood pressures. 3 HCT consistently brought about significant increases in serum uric acid and significant decreases in serum potassium; both doses of MK-196 produced similar but less frequent and smaller changes in both of these parameters. 4 Both doses of MK-196 brought about significant decreases in body weight at Weeks 3 and 4 of drug treatment. 5 Patients taking MK-196 reported fewer adverse clinical reactions (10 mg = 15%; 15 mg = 13% than those taking HCT (21%). 6 MK-196 may offer a therapeutic advantage over HCT as an antihypertensive agent for use in the treatment of mild to moderate, essential hypertension.

Suppression of puerperal lactation with an ergot alkaloid: a double-blind study.

A double-blind trial was performed in 60 women to establish the effectiveness of an ergot alkaloid, 2-Br-alpha-ergocryptine (ergocryptine; CB 154), in suppressing puerperal lactation and to compare it with stilboestrol and a placebo. At the doses selected ergocryptine and stilboestrol were equally effective.

Treatment of non-puerperal galactorrhoea with an ergot alkaloid.

Three patients suffering from non-puerperal galactorrhoea over periods ranging from two months to six years were treated with an ergot alkaloid, 2-Br-alpha-ergocryptine (CB 154). In all three cases the galactorrhoea was terminated. The apparent prolactin antagonism exhibited by this compound is discussed.