Antagonism of aldosterone in normal subjects by Ro 12-2503 and spironolactone.

The potency and efficacy of a single dose of a new aldosterone antagonist, potassium 17 a-hydroxy-6 beta, 7 beta-methylene-3-oxo-D-homo-17a alpha-pregna-4,16-diene-21-carboxylate (Ro 12-2503), in reversing the renal effects of exogenous aldosterone were compared to those of spironolactone, and placebo. The study was performed according to double-blind and crossover procedure in six healthy male subjects. Both drugs, spironolactone and Ro 12-2503, did not completely antagonize the effects of aldosterone. The efficacy of Ro 12-2503 in terms of the urinary Na+/K+ ratio and the urinary Na+ concentration was less than that of spironolactone. Spironolactone produced a slightly greater natriuresis, but the difference was not significant. The method described, based on standard bioassay techniques permits a comparison of the two drugs, and may prove useful in the screening and evaluation of aldosterone antagonists.

[Management of supraventricular and ventricular arrhythmias with the intravenous administration of the calcium antagonist Tiapamil (Ro 11-1781) (author's transl)]. / Die parenterale Behandlung von supraventrikulären und ventrikulären Herzrhythmusstörungen mit dem Kalziumantagonisten Tiapamil (Ro 11-1781).

27 cardiac patients with a mean age of 58.5 years (S.D. +/- 9.43) were treated in the coronary care unit with tiapamil, a new Ca2+ antagonist, by intravenous infusion. The following arrhythmias were identified: ventricular premature complexes (VPCs, Lown class 3--5) in 15 patients, supraventricular premature complexes (SVPCs) in 6 patients, and mixed VPCs (Lown grade 5) plus SVPCs in 6 patients. ECGs and hemodynamic parameters were continuously monitored prior to, during and up to 24 hours after the therapy. In patients with VPCs, the median frequency of VPCs decreased from 612.0 to 64.0 at the 3rd hour of therapy (p less than 0.01). Between the 13th and the 24th hour after tiapamil, without therapy the median VPCs increased to 459.0. The median "VPCs/sinusal" beats ratio was decreased from 0.125 to 0.0108 (p less than 0.01) at the 3rd hour and returned to 0.1029 from the 9th to the 20th hour after stopping tiapamil. The results in the patients with SVPCs, or with VPCs + SVPCs were similar. Tiapamil did not affect the central venous pressure and decreased the median blood pressure from 130/80 to 110/75 mm Hg (p less than 0.10). The effects of tiapamil against all types of cardiac arrhythmias can therefore be defined as good. 1/27 patients presented hypotension that required therapy with dopamine, and mild subjective complaints (mainly headache) were reported in 6 patients. No complications occurred. The results show that tiapamil is effective both against SVPCs and VPCs, and thus its spectrum of action differs from that of other Ca2+ antagonists.

Antiarrhythmic effect of the calcium antagonist tiapamil (Ro 11-1781) by intravenous administration in patients with coronary heart disease.

Twenty coronary patients with a median age of 76 years were treated in the coronary care unit with tiapamil, a new Ca2+ antagonist, by intravenous infusion (until December, 1979, the generic name was dimeditiapramine). The following arrhythmias were identified: atrial fibrillation with ventricular rate greater than 95 beats/min (5 patients); supraventricular premature complexes (SVPC) (4 patients); and ventricular premature complexes (VPC), Lown grades 2-4 (15 patients). Electrocardiograms and hemodynamic parameters were continuously monitored prior to, during, and after the therapy. In patients with atrial fibrillation, sinus rhythm was not restored, but tiapamil decreased the ventricular rate by 54%. In patients with VPC, the median frequency of VPC decreased from 310.5 before tiapamil to 32.5 beats/h at the fourth hour of therapy (p less than 0.01). The median ectopic/sinus beat ratio decreased from 0.083 (pretreatment) to 0.008 at the fourth hour of infusion (p less than 0.10). In one of the patient with an insufficient decrease in the number of VPC, the VPOC changed from class 4a (pretreatment) to class 2 (during the therapy), returning to class 4a after the infusion was stopped. Tiapamil reduced the median systolic and diastolic blood pressures by 8.3 and 7.1%, respectively (p less than 0.05), the third hour. Hypotension and bradycardia were observed in 5/20 patients. The results show that tiapamil is effective against both supraventricular and ventricular arrhythmias, and thus its spectrum of action differs from that of other calcium antagonists.