Pearce P C, Halsey M J, Maclean C J, Ward E M, Pearson J, Henley M, Meldrum B S
Anaesthesia/HPNS group, Clinical Research Centre, Harrow, UK.
Brain Res. 1993 Sep 17;622(1-2):177-84. doi: 10.1016/0006-8993(93)90817-7.
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 occurring 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.
在非人灵长类动物阿拉伯狒狒中，研究了一种新型口服活性竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（DL-(E)-2-氨基-4-甲基-5-膦酰基-3-戊烯酸乙酯）CGP 39551对高压神经综合征（HPNS）的神经生理效应。六只动物在氦氧环境中两次暴露于81个绝对大气压的最大压力下。一次暴露在压缩前24小时口服100 mg/kg的CGP 39551进行预处理，另一次用等量的赋形剂（在这种情况下为水）进行预处理。与对照组相比，在高于31个绝对大气压的压力下，CGP 39551显著改善了HPNS的症状，并防止了在更高压力下出现严重症状。然而，低压下轻度症状的起始压力未受影响。在脑电图变化中，CGP 39551可防止压力引起的δ波振幅降低，但不能防止7-9 Hz频段振幅增加。结论是，CGP 39551可能在HPNS的预防性治疗中发挥重要作用。
