Pharmacological studies on talampicillin hydrochloride (Japanese)

Abstract

Behavioural observations in mice, rats, cats and dogs revealed sedation due to high doses of talampicillin hydrochloride (TAPC). Repeated doses for 8 days, as well as a single oral administration of TAPC both caused sedation in rats. Barbital induced sleeping time was prolonged with 1000 mg/kg p.o. of TAPC in mice. In EEG studies, 100 mg/kg i.v. of TAPC enhanced slow wave activity of cortical and subcortical area except for the hippocampus. The threshold of arousal responses to electrical stimulation of the mesencephalic reticular formation was slightly elevated in some cats. No abnormal EEG response to sonic stimulation and calling was observed. A dose producing convulsions in 50% of mice after intracerebral application of TACP was almost equal to that of ampicillin, and was about 20 times that of penicillin G potassium. In anesthetized dogs, 3 mg/kg i.v. of TACP caused a reduction of blood pressure and an increase in heart rate. Hypotension and increases in respiratory rate and femoral blood flow were elicited by 10-100 mg/kg i.v. Heart rate tended to increase with low doses and to decrease with high doses. With a dose of 300 mg/kg i.v., two of three dogs died. When administered into the duodenum, TAPC caused a reduction of blood pressure and a decrease in heart rate with a dose of 10 g/kg, and death with a dose of 30 g/kg. Intravenous injection of phthalaldehydic and α hydroxy o toluic acid, metabolites of TAPC, reduced blood pressure, and increased femoral blood flow and respiratory rate in a dose range of from 30 to 300 mg/kg i.v. Antagonizing activities of TAPC (3 x 10 -5 - 10 -4 g/ml) against several spasmogens were detected in isolated ileum of guinea pigs. Both contractility and rhythmicity of isolated rat uterus were suppressed at 10 -7 - 10 -6 g/ml of TAPC. No measurable effects of TAPC were obtained in the following experiments; anticonvulsive tests (maximal electroshock, pentetrazol, and strychnine), tremorine induced tremor, conditioned avoidance response, analgesic activity, rectal temperature, neuromuscular function, surface anesthesia, contractility of nictitating membrane, gastrointestinal propulsion, irritation of gastric mucosa, urine excretion, eye irritancy and antigenicity.