Pc. Pearce et al., THE ORALLY-ACTIVE NMDA RECEPTOR ANTAGONIST CGP-39551 AMELIORATES THE HIGH-PRESSURE NEUROLOGICAL SYNDROME IN PAPIO-ANUBIS, Brain research, 622(1-2), 1993, pp. 177-184
The neurophysiological effects of a novel, orally active, competitive
N-methyl-D-aspartate (NMDA) receptor antagonist (DL-(E)-2-amino-4-meth
yl-5-phosphono-3-pentenoic acid ethyl ester), CGP 39551, on the high p
ressure neurological syndrome (HPNS) were investigated in the non-huma
n primate Papio anubis. Six animals were exposed to maximum pressures
of 81 ATA in a helium and oxygen environment, on two occasions. One ex
posure was pretreated orally with CGP 39551 100 mg/kg 24 h before comp
ression, the other pretreated with an equivalent volume of vehicle, in
this case water. CGP 39551 significantly ameliorated the signs of HPN
S, compared with controls, at pressures above 31 ATA and prevented the
severe signs from occurring at the higher pressures. Onset pressures
of the mild signs at low pressures were, however, unaffected. Among EE
G changes, the pressure induced reduction in delta wave amplitude was
prevented by CGP 39551, but the increase in the amplitude of the 7-9 H
z band was not. It is concluded that CGP 39551 may play an important r
ole in the prophylactic treatment of HPNS.