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N-methyl-D-aspartate antagonists and drug discrimination.

机译：N-甲基-D-天冬氨酸拮抗剂和药物鉴别。

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Excitatory amino acids (EAA), such as glutamate, are thought to be involved in various disorders (e.g., ischemic brain damage, epilepsy, Parkinson's disease), and EAA antagonists have been suggested as potential treatments for these disorders. Phencyclidine (PCP), with produces psychotomimetic effects in humans, has antagonist properties at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors that have been suggested to underlie some of its actions. This suggestion, and concern about possible psychotomimetic activity, has stimulated research aimed at examining to what extent the behavioral profile of other NMDA antagonists resembles that of PCP. Drug discrimination (DD) is prominent among the procedures used to carry out such comparisons. The results of clinical studies with NMDA antagonists provide feedback about the predictive validity of the DD procedures used to characterize their preclinical behavioral profile. Further, DD is used also to examine the ability of compounds to attenuate the discriminative stimulus (DS) effects of PCP-type drugs, and results of such studies have been suggested to provide evidence of antipsychotic potential. Finally, although many instances of intermediate responding in DD can be explained by low efficacy at the receptors that mediate the DS effects of the training drug, certain outcomes produced by PCP-type drugs do not offer valid measures of efficacy, and require more detailed behavioral analyzes.
机译：谷氨酸等兴奋性氨基酸（EAA）被认为与多种疾病（例如缺血性脑损伤，癫痫，帕金森氏病）有关，而EAA拮抗剂已被建议作为这些疾病的潜在治疗方法。苯环利定（PCP）在人类中会产生拟精神病作用，它对谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型具有拮抗作用，已被认为是其某些作用的基础。这个建议以及对可能的拟精神活性的关注，已经引发了旨在研究其他NMDA拮抗剂的行为特征在何种程度上类似于PCP的研究。在进行此类比较的程序中，药物歧视（DD）尤为突出。 NMDA拮抗剂的临床研究结果提供了有关用于表征其临床前行为特征的DD程序的预测有效性的反馈。此外，DD还用于检查化合物减弱PCP型药物的歧视性刺激（DS）效果的能力，并且已表明此类研究的结果可提供抗精神病药的证据。最后，尽管在DD中发生中间反应的许多情况可以通过介导训练药物的DS效应的受体功效低下来解释，但PCP型药物产生的某些结局不能提供有效的功效指标，并且需要更详细的行为分析。

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