Leander J D, Lawson R R, Ornstein P L, Zimmerman D M
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Brain Res. 1988 May 10;448(1):115-20. doi: 10.1016/0006-8993(88)91107-9.
N-Methyl-D-aspartic acid (NMDA) produced a dose-related increase in lethality in mice, with 200 mg/kg (i.p.) effecting 100% lethality. Upon daily dosing, acutely sublethal doses of NMDA produced deaths. This NMDA-induced lethality was stereoselective; N-methyl-L-aspartic acid had no effects at doses as high as 400 mg/kg. Moderate doses of phencyclidine (PCP) and drugs having PCP-like behavioral effects blocked the NMDA-induced lethality. Other classes of psychoactive drugs, including opioids, anticonvulsants and antipsychotics, were ineffective in preventing NMDA-induced lethality. The potency of PCP-like drugs to block the NMDA-induced lethality correlates highly with the dose necessary to produce PCP-like catalepsy and PCP-like discrimination in pigeons. These data support the hypothesis that PCP-like drugs produce many of their effects by impairing the normal functioning of the NMDA-defined excitatory neurotransmitter receptor in the central nervous system.
N-甲基-D-天冬氨酸（NMDA）可使小鼠的致死率呈剂量依赖性增加，腹腔注射200毫克/千克时致死率达100%。每日给药时，急性亚致死剂量的NMDA可导致死亡。这种NMDA诱导的致死性具有立体选择性；N-甲基-L-天冬氨酸在高达400毫克/千克的剂量下无作用。中等剂量的苯环利定（PCP）及具有类似PCP行为效应的药物可阻断NMDA诱导的致死性。其他类别的精神活性药物，包括阿片类药物、抗惊厥药和抗精神病药，在预防NMDA诱导的致死性方面无效。类似PCP的药物阻断NMDA诱导的致死性的效力与在鸽子中产生类似PCP的僵住症和类似PCP的辨别所需的剂量高度相关。这些数据支持这样的假说，即类似PCP的药物通过损害中枢神经系统中由NMDA定义的兴奋性神经递质受体的正常功能而产生其许多效应。
