The orally active NMDA receptor antagonist CGP 39551 ameliorates the high pressure neurological syndrome in Papio anubis

Abstract

The neurophysiological effects of a novel, orally active, competitive N-methyl- d-aspartate (NMDA) receptor antagonist ( dl-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid ethyl ester), CGP 39551, on the high pressure neurological syndrome (HPNS) were investigated in the non-human primate Papio anubis. Six animals were exposed to maximum pressures of 81 ATA in a helium and oxygen environment, on two occasions. One exposure was pretreated orally with CGP 39551 100 mg/kg 24 h before compression, the other pretreated with an equivalent volume of vehicle, in this case water. CGP 39551 significantly ameliorated the signs of HPNS, compared with controls, at pressures above 31 ATA and prevented the severe signs from occuring at the higher pressures. Onset pressures of the mild signs at low pressures were, however, unaffected. Among EEG changes, the pressure induced reduction in delta wave amplitude was prevented by CGP 39551, but the increase in the amplitude of the 7–9 Hz band was not. It is concluded that CGP 39551 may play an important role in the prophylactic treatment of HPNS.