suloctidil and Hypoxia

In the treatment of cerebral infarction, it is important to select drugs for inhibiting development of the pathology. In order to select markedly effective drugs among many drugs, it is possible to grasp the outline of drug effects by means of an experimental system with simplicity and regularity--a screening test. In the present study, we induced a hypoxic load by exposing mice to a gas mixture consisting of 4% O2 and 96% N2, and investigated the effects of various kinds of drugs with reference to the survival time(ST: mean +/- SE), the time until the respiratory arrest of the mice. In the control group (n = 110), ST was 170 +/- 6 sec, with a normal distribution, and no mice that survived for eight minutes or more after the load were found. In contrast, ST was 1,833 +/- 487 sec in the suloctidil-treated group (12.5 mg/kg, n = 11), 1,160 +/- 342 sec in the vitamin E group (200 mg/kg, n = 15), 602 +/- 74 sec in the pentobarbital group (50 mg/kg, n = 12) and 2667 +/- 452 sec in the phenytoin group (100 mg/kg, n = 10). On the other hand, no prolongation of ST was found in the groups to which vitamin C, coenzyme Q, cytochrome c, betamethasone, mannitol or germanium-132 were administered. The ratio of the mice that survived for one hour or more after the load was 0% in the control group, 45.5% in the suloctidil group (12.5 mg/kg), 23.5% in the vitamin E group (200 mg/kg), 0% in the pentobarbital group (50 mg/kg) and 70% in the phenytoin group (100 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Atmosphere Exposure Chambers; Cerebral Infarction; Drug Evaluation, Preclinical; Hypoxia; Male; Mice; Pentobarbital; Phenytoin; Suloctidil; Vitamin E

A systematic study of the hypobaric hypoxia method was carried out, using a wide range of vasodilators and metabolic modifiers. In general cerebral metabolic modifiers have a more effective antihypoxic action than cerebral vasodilators. After a discussion, the conclusion is that hypobaric hypoxia is useful as an initial screening procedure.

Topics: Animals; Atmospheric Pressure; Brain; Cerebrovascular Circulation; Disease Models, Animal; Hypoxia; Isoxsuprine; Male; Mice; Motor Activity; Suloctidil; Temperature; Vasodilator Agents

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.

Topics: Animals; Brain; Brain Chemistry; Cerebrovascular Circulation; Energy Metabolism; Glucose; Hypoxia; Male; Mice; Mice, Inbred Strains; Propanolamines; Pyrithioxin; Suloctidil

Transient anoxia obtained in curarized rats by momentary stopping of the artificial respiration (80 sec duration) induced a failure of the cerebral electrical activity. This effect was characterized by cessation of the spontaneous unitary discharge of cortical neurons and reduction of amplitude of somatosensory evoked potentials. Pretreatment with flunarizine (10 mg/kg/os) or suloctidil (50 mg/kg/os) induced a distinct improvement of the resistance to anoxia and of the recovery of the cerebral electrical activity.

Topics: Animals; Brain; Calcium Channel Blockers; Cinnarizine; Electrophysiology; Evoked Potentials; Flunarizine; Hypoxia; Male; Neurons; Rats; Suloctidil