1982 Volume 35 Issue 9 Pages 2139-2154
General pharmacological studies on T-1982 produced the following results.
On central nervous system, subcutaneous injection of T-1982 at dose of 2,000 mg/kg hastened the onset of pentetrazole-induced tonic extensor in mice.T-1982 had no effect on spontaneous motor activity, pentobarbital hypnosis, body temperature or EEG in mice or rabbits, and also did not show moter incoordinate, anticonvulsive or analgesic activity in mice at intravenous doses of 250, 1,000 mg/kg or subcutaneous doses of 500-2,000
mg/kg. On motor and sensory nervous systems, no effect of T-1982 was noted on spinal reflex, neuromuscular junction, conduction anesthesia or surface anesthesia in rats or rabbits.
On respiratory, cardiovascular and autonomic nervous systems, T-1982 caused transient increase of respiratoryrate, slight hypotension and transient increase of femoral blood flow in dogs at intravenous doses of 250-1,000mg/kg.However, it caused a slight hypertensive tendency in rabbits.Heart rate and ECG in dogs or rabbits, blood pressure response to epinephrine, isoproterenol, acetylcholine or histamine in dogs, nictitating membranein cats and pupil size in mice were not affected after intravenous injection of T-1982.No effect was found onisolated guinea pig atrium or rabbit descending aorta following T-1982 application.
On renal function in rats, T-1982 caused an increase of PSP excretion but had no effect on urine volume or electrolytes excretion at intravenous doses of 250-1,000 mg/kg.
T-1982 prolonged bleeding time in mice at intravenous doses of 500-1,000 mg/kg, but did not show hemolytic property and inhibitory activity on blood coagulation or platelet aggregation in vitro experiments.
Spontaneous movement and tone of isolated stomach, ileum, colon, uterus, was deferens or trachea and acetylcholine-, histamine-, nicotine-or barium chloride-induced contraction of ileum were not affected following T-1982 application.Intestinal propulsion of barium meal in mice, gastric secretion and carrageenin-induced edema in rats were not affected after intraveonus injection of T-1982.
T-1982 increased bile secretion in rats dose-dependently at intravenous doses of 31.3 125 mg/kg.The local irritative activity of T-1982 in rats was slightly milder than cefoxitin and moderately milder than cefmetazole after intradermal injection.
In conclusion, these results suggest that T-1982 would not cause any adverse effects at its estimated clinical doses of 10-20 mg/kg (500-1,000 mg/man).
