Abstract
The protective effects of TJ-8007 (Tsumura-Zokumeito, Traditional chinese medicine) against cerebral anoxia were investigated with various experimental models in mice and rats. 1) In histotoxic anoxia, TJ-8007 (0.3 ?? 3.0g/kg, p.o.) dose-dependently demonstrated a protective effect on coma induced by a sublethal dose of KCN (1.8 mg/kg, i.v.) in mice. Ifenprodil (30 mg/kg, p.o.) tended to reduce the coma time, but papaverine (100 mg/kg, p.o.) showed a negative effect. 2) TJ-8007 (0.3 ?? 3.0 g/kg, p.o.) dose-dependently tended to prolong the survival time of mice subjected to a lethal dose of KCN (3.0 mg/kg, i.v.), TJ-8007 also improved the survival rate at the dose of 3.0 g/kg. Ifenprodil (30 mg/kg, p.o.) or papaverine (100 mg/kg, p.o.) exerted a similar effect on the survival time, but did not affect the mortality. 3) In the normobaric hypoxia with a gas mixture of 96% N2 and 4% O2, TJ-8007 (0.3 ?? 3.0g/kg, p.o.) did not affect the survival time of mice. On the other hand, papaverine (100 mg/kg, p.o.) prolonged the survival time, and phenytoin (100 mg/kg, p.o.) showed a marked protective effect, but ifenprodil (30 mg/kg, p.o.) produced an adverse effect. 4) In the asphyxic anoxia induced by stopping artificial respiration of immovable rats, TJ-8007 (1.0, 3.0 g/kg, p.o.) showed a protective effect on the fall of systemic blood pressure and on the decline of heart rate; furthermore, it dose-dependently prolonged the disappearance time of cortical activity. Also, phenytoin (100 mg/kg, p.o.) tended to protect against the fall of blood pressure and prolonged the cortical resistance time. However, these protective effects of phenytoin were less than that of TJ-8007 at the dose of 3.0 g/kg. Ifenprodil (30 mg/kg, p.o.) did not affect the cortical resistance time. As described above, TJ-8007 demonstrated protective effects in a dose-dependent manner against the brain damages induced by cerebral anoxia.
