The protective effect of adenosinergic agents, Ro 5-4864 and carbamazepine against hypoxic stress-induced neurotoxicity in mice.

Mice subjected to hypoxic stress resulted in increased respiratory rate, tremor and convulsions followed by death. The latencies for convulsion and death following hypoxic stress were 33.29 +/- 1.20 and 34.36 +/- 1.16 min, respectively. In the present study effects of adenosinergic agents Ro 5-4864, a "peripheral-type" benzodiazepine receptor agonist, and carbamazepine were studied on hypoxic stress-induced neurotoxicity. Adenosinergic agents such as adenosine, 2-chloroadenosine, N6-cyclohexyladenosine and dipyridamole increased the latencies for convulsions and death due to hypoxia. Theophylline (50 mg/kg i.p.), an adenosine receptor antagonist, reversed this protective effect of adenosinergic agents. Pretreatment with Ro 5-4864 (10, 20 mg/kg i.p.) also offered theophylline (50 mg/kg, i.p.)-sensitive protection against hypoxic stress. Similarly, carbamazepine treatment (10-30 mg/kg, i.p.) significantly prolonged the latencies for convulsion and death following hypoxic stress. Prior treatment with theophylline (50 mg/kg, i.p.) reversed this protective effect of carbamazepine, indicating the possible involvement of adenosinergic mechanism in the observed protective effect of carbamazepine. These results indicate that the adenosinergic mechanism may be responsible for the observed neuroprotective effect of these agents against hypoxia.