Elliott K, Kest B, Man A, Kao B, Inturrisi C E
Department of Pharmacology, Cornell University Medical College, New York, New York 10021, USA.
Neuropsychopharmacology. 1995 Dec;13(4):347-56. doi: 10.1016/0893-133X(95)00083-P.
This laboratory perspective reviews the pharmagologic approaches that have been used in preclinical animal models to demonstrate the ability of competitive (LY274614) and noncompetitive (MK801 and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists to attenuate or reverse the development of morphine tolerance. We provide additional data to support previous observations that these NMDA antagonists modulate morphine (mu) opioid tolerance but do not affect U50488H (kappa 1) opioid tolerance. A strategy, which utilizes efficacy as an NMDA receptor antagonist and clinical safety, provides the basis for a discussion of the clinical potential of dextromethorphan, ketamine, and felbamate as modulators of opioid tolerance in pain patients or opioid addicts. The potential use of NMDA receptor antagonists and nitric oxide synthase (NOS) inhibitors in neuropathic pain is also discussed.
本实验室视角回顾了在临床前动物模型中所采用的药理学方法，这些方法用于证明竞争性（LY274614）和非竞争性（MK801及右美沙芬）N-甲基-D-天冬氨酸（NMDA）受体拮抗剂减弱或逆转吗啡耐受性发展的能力。我们提供了更多数据以支持先前的观察结果，即这些NMDA拮抗剂可调节吗啡（μ）阿片类药物耐受性，但不影响U50488H（κ1）阿片类药物耐受性。一种利用作为NMDA受体拮抗剂的功效及临床安全性的策略，为讨论右美沙芬、氯胺酮和非氨酯作为疼痛患者或阿片类药物成瘾者阿片类药物耐受性调节剂的临床潜力提供了基础。同时也讨论了NMDA受体拮抗剂和一氧化氮合酶（NOS）抑制剂在神经性疼痛中的潜在用途。
