The tolerance and diuretic properties of torasemide after oral or intravenous administration to healthy volunteers were studied. Six groups, each of 6 subjects, were given single rising oral doses ranging from 10 to 100 mg; 8 subjects received ascending i.v. doses on alternate days, ranging from 2.5 to 80 mg. At the highest oral doses investigated (80 mg and 100 mg) a number of volunteers complained of cramps in the knees, calves and feet. These symptoms were generally of short duration. Similar effects were not encountered during the intravenous study. There were no significant changes in ECG. Some significant drug-related changes were encountered in the within-study biochemistry and haematology assessments. Torasemide proved to be a potent diuretic following oral administration at all the doses investigated and following intravenous administration at all doses except 2.5 mg. A linear relationship existed between the urine output and the logarithm of the dose, and both sodium and chloride excretion were linearly correlated with urine volume. The rate of potassium excretion was markedly lower than that of sodium and chloride and was linearly correlated with the logarithm of the urine volume. Torasemide was well tolerated from all perspectives studied. It showed a potent diuretic property, and was equally effective by the oral and intravenous routes.

Ro 11-2465, a cyanide derivative of imipramine with serotonin uptake inhibitory properties, was investigated in six healthy volunteers for its effect on serotonin concentration in blood platelets. The initial dose was 1 mg daily, the maximum dose of 3 mg being reached on day 3 and maintained for 7 days. A significant decrease in the platelet serotonin concentration was not observed until 3 days after the start of drug administration, after which depletion was rapid. After 5 days of treatment, the reduction was about 80% compared to pre-drug level. Serotonin restoration after drug withdrawal was very slow, and 5 days after discontinuation, it was still 70% below its baseline level.

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