Abstract
Pharmacological effects of josamycin propionate (JM-P), a new macrolide antibiotic derivative, were additionally investigated and the following results were obtained.
1. When JM-P was administered orally at doses up to 1,000 mg/kg, no measurable effects were observed in rotarod performance test, traction method, fighting behavior, tremorine test in mice and conditioned avoidance response of rats. Both monosynaptic and polysynaptic reflexes were slightly increased with JM-P 10 mg/kg given intravenously in cats. On injecting intracerebrally, JM-P gave rise to abnormal gait, clonus and jumping in mice and 50% convulsion dose was 11.0 mg/kg.
2. No influence was detected on constriction of isolated guinea-pig tracheal muscle produced by acetylcholine, while an inhibition was observed on that of isolated guinea-pig was deferens caused by adrenaline at 1×10-4g/ml of JM-P. A slight inhibition was seen on contractions of isolated guinea-pig ileum elicited by ACh or barium chloride at a high concentration (1×10-3g/ml) of JM-P. JM-P at 1×10-4 g/ml or higher doses caused dose dependent decrease in spontaneous movement of isolated non-gravid rat uterus. No effects were seen on digestive propulsion of mice after oral administration of JM-P at a dose of 1,000 mg/kg.
3. Dose-dependent decrease in heart rate and blood pressure with increased blood flow of carotid and femoral artery were observed at doses of not less than 10 mg/kg of JM-P given intravenously in anesthetized dogs. The hypotensive effect induced by JM-P given intravenously was not inhibited by the pretreatment with atropine or diphenhydramine in anesthetized cats. JM-P at a dose of 100 mg/kg given intravenously gave rise to respiratory inhibition, decreased heart rate and blood pressure, and drop of wave height in P, Q and ST, and prolongation of P-Q, P-R, P-P intervals in anesthetized dogs. These changes disappeared after 90 minutes. On isolated guineapig atria, a depression of amplitude of contraction and a decrease of heart rate were observed at 1×10-4g/ml or higher doses of JM-P, and no influence was seen on cardiac promotion induced by noradrenaline with 1×10-4g/ml of JM-P.
4. No effects were observed on hemolytic resistance and coagulation of whole blood in rabbits at 300 mg/kg of JM-P given orally.
5. On urine volume and pH, and urinary excretion of sodium or pottasium, no influence was seen in rats with 1,000 mg/kg of JM-P given orally.
