Protective effects of vinpocetine and structurally related drugs on the lethal consequences of hypoxia in mice.

Vinpocetine has been compared with 3 structurally related drugs for activity in protecting mice from hypoxia-induced lethality upon i.p. administration. In order of potency, vinpocetine (ED50 = 16.6 mg/kg), 1-eburnamonine (ED50 = 21.0 mg/kg), vinconate (ED50 approximately 25 mg/kg), and vincamine (ED50 = 47.0 mg/kg) increased the number of mice surviving an 80 sec exposure to 100% nitrogen gas. Furthermore, the antihypoxic effects of these drugs were not due to an induced hypothermia. All of the drugs, with the exception of vinconate, exhibited a monotonic dose-response curve and caused 100% survival at some dose. The antihypoxic effects with vinpocetine and related drugs in this model correlate with protective effects observed in animal models of cerebral ischemia and with therapeutic effects in patients with compromised cerebral blood flow. The possible mechanisms of action of these drugs are discussed.