Effect of MK-801 and its interaction with adenosinergic agents and carbamazepine against hypoxic stress-induced convulsions and death in mice.
Effects of MK-801, adenosinergic agents and carbamazepine were investigated against hypoxic stress-induced convulsions and death in mice. MK-801, a N-methyl D-aspartate antagonist, offered a significant protective effect against hypoxic convulsions. Adenosinergic agents such as adenosine, 2-chloroadenosine, N6-cyclohexyladenosine and dipyridamole produced theophylline-sensitive protective effect as they dose-dependently prolonged the latencies for onset of convulsions and death. Pretreatment with adenosinergic agents and MK-801 markedly enhanced the protective effect of the stable analogs of adenosine namely, 2-chloroadenosine and N6-cyclohexyladenosine. However, pretreatment with combination of MK-801 and adenosine or dipyridamole did not show enhanced protective effect. Carbamazepine also exhibited dose-dependent theophylline-sensitive protective effect. The pretreatment with combination of carbamazepine and MK-801 showed significantly enhanced protective effect. The observed enhanced protective effect of MK-801 and adenosinergic agents was reversed by pretreatment with theophylline. These results indicate the possible involvement of adenosinergic mechanisms in preventing hypoxic stress-induced convulsions and the role of NMDA receptors in hypoxia-induced convulsions and death as MK-801 not only showed effect per se but also potentiated the response due to adenosinergic agents.
Thorat
S N
SN
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Kulkarni
S K
SK
D015762:2-Chloroadenosine / Q000627:therapeutic use; D000241:Adenosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D002220:Carbamazepine / Q000627:therapeutic use; D004176:Dipyridamole / Q000633:toxicity; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D008297:Male; D051379:Mice; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D013312:Stress, Physiological / Q000150:complications; D013806:Theophylline / Q000494:pharmacology
D015762:2-Chloroadenosine; D002220:Carbamazepine; C027513:N(6)-cyclohexyladenosine; D004176:Dipyridamole; D016291:Dizocilpine Maleate; D013806:Theophylline; D000241:Adenosine