A NEW ANTIBIOTIC, JOSAMYCIN. VII STUDIES ON PHARMACOLOGY

Abstract

Multidimentional observations in mice indicated sedative activity of josamycin, and several sympathomimetic or parasympathomimetic profiles at higher doses. Behavior changes about the same as in mice were also observed in cats. Josamycin caused drop of the blood level and depression of the respiration in anesthetized cats injected with 100mg/kg intravenously. Electrocardiograms indicated various kinds of effects, such as prolongation of PP-and PQ-intervals and arrhythmia at 1.0mg/kg. On isolated heart preparation of guinea-pig, an increase in the coronary flow, transient depression of the amplitude of contraction and slight decrease of heart rate were observed at1mg/kg and higher doses of josamycin. No definite activity was observed on the uterus preparation of rat. Josamycin (0.01mg/ml and higher concentration) dose-dependent decrease in contractility of the isolated ileum of rabbit. A nonspecific antispasmolytic effect against acetylcholine, histamine and barium was also observed. In electroencephalogram, there was no convulsion pattern, but slow waves of low amplitude were observed. Josamycin did not cause any neuromuscular blocking effect on the indirectly stimulated diaphragm-phrenic nerve preparation of rat. The body temperature remained unaltered in rabbit injected various doses of josamycin. Only higher doses of josamycin decreased urinary excretion of rat. Josamycin, at 100mg/kg intradermally injected had irritant effect on the skin of rabbit almost equivalent to 0.1mg/ml of histamine.