N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development.
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.
Elliott
K
K
Department of Pharmacology, Cornell University Medical College, New York, New York 10021, USA.
Kest
B
B
Man
A
A
Kao
B
B
Inturrisi
C E
CE
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D003915:Dextromethorphan / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D011759:Pyrrolidines / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000187:drug effects*
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D009294:Narcotics; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C070935:LY 274614; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; D019001:Nitric Oxide Synthase