Tsuneyoshi Tanabe

ON THE SUBACUTE TOXICITY OF LABETALOL (AH5158) : A COMBINED α-AND β-ADRENOCEPTOR-BLOCKING AGENT

Subacute toxicity and recovery tests of labetalol hydrochloride, α-and β-adrenoceptor blocking agent, were carried out using male and female Wistar strain rats. The drug was orally administered at 50, 150, 450 or 1000 mg/kg/day for 1 month. In all the drug-treated groups, increase in salivation was observed from immediately to 15 minutes after dosing through the treatment period. Eight of the 10 males and 9 of the 10 females in the group treated with 1000mg/kg/day died of intoxication. Suppresion of body weight gain was observed in male rats in the 450 and 1000 mg/kg/day groups and in female rats in the 1000 mg/kg/day group. In the 150 mg/kg/day and higher dose groups, water comsumption showed a tendency to increase as compared with that of control group. Increase in urine volume was observed in female rats in the 450 mg/kg/day group. In the serum biochemical examinations, slight elevation in potassium levels was noted in the 150 and 450 mg/kg/day groups. In histopathological findings, some abnormalities were found in organs were; congestion and hypremia of various organs due to vasodilation, swelling of parenchymatous cells in liver and kidneys, and loose arrengement and change in the thickness of muscle fibers in cardiac and skeletal muscles. None of these abnormal findings was found in any examination in recovery tests. From these results, it was suggested that maximum non-toxic dose of labetalol hydrochloride was about 150 mg/kg/day in male and female rats.

On the influence of rescinnamine, deserpidine and syrosingopine on the respiratory function of the guinea pig heart muscle mitochondria

Rescinnamine, deserpidine, syrosingopine and reserpine were injected subcutaneously at a dose of 5 mg/kg respectively into guinea pigs 24 hours prior to sacrificing. Respiratory function of the heart mitochondria was tested by using the polarographic technique with a rotating electrode. Deserpidine and reserpine showed a remarkable decrease in QO2 at state 3 and an increase in QO2 at state 4 on oxidative phosphorylation. Accordingly, the value of respiratory control was markedly lowered as compared with that of control. ADP/O ratio was not significantly lowered by deserpidine and reserpine. Syrosingopine and rescinnamine induced a decrease in QO2 at state 3 and an insignificant change or poorly significant increase in QO2 at state 4. The respiratory control was significantly lowered by these two alkaloids. Byin vitro experiments, it was demonstrated that rescinnamine produced a different type of obstruction on the oxidative and phosphorylative system of the heart mitochondria. A discussion was made on the difference between results obtained byin vivo andin vitro experiments.