Abstract
It has been demonstrated that suloctidil [erythro-1-(4-isopropylthiophenyl)-2-n-octylaminopropanol] has a protective effect against cerebral hypoxia to elongate the survival time of mice subjected to normobaric hypoxia (96% N2+4% O2 gas mixture). In this study, further experiments were done to elucidate the mechanism of protection against cerebral hypoxia with a variety of experimental models. Pretreatment (30 min) with suloctidil (12.5-50 mg/kg, i.p.) increased the number of gasping in the decapitated head of mouse as a complete ischemic model. Pyrithioxine (25, 50 mg/kg, i.p.) or cinnarizine (50, 100 mg/kg, i.p.) did not increase the gasping number. In the histotoxic anoxia with KCN (4 mg/kg, i.v.) in mice, suloctidil showed 30.8% and 46.2% survival rates at the doses of 25 and 50 mg/kg, i.p., respectively. Concerning this result, it has been revealed that suloctidil did not have any methemoglobin formation liability in rats (unpublished). Pyrithioxine did not show such protection following the injection of 12.5-50 mg/kg, i.p.. Suloctidil (3.0-50 mg/kg, i.p.) and pyrithioxine (3.0, 10 mg/kg, i.p.) significantly prolonged the survival time of mice subjected to hypobaric hypoxia (210 mmHg). In this cerebral hypoxia model, suloctidil kept glucose at a significantly higher level and lactate at a lower level in the brain of mice that were administered this drug than the control group. ATP was kept at higher level after suloctidil than the control under hypobaric hypoxia. Taking these evidences together, it can be concluded that suloctidil exerts its cerebral anti-hypoxic effect through cerebral glucose metabolism coupled with oxidative phosphorylation to yield the high energy substance ATP in a variety of models tested in this study. The fact obtained in this study, together with increase in cerebral blood flow by suloctidil, may also elucidate the protective effect of suloctidil against cerebral hypoxia.
