Effects of competitive and noncompetitive antagonists of the N-methyl-D-aspartate receptor on the analgesic action of delta 1- and delta 2-opioid receptor agonists in mice.
1. The effects of MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and LY 235959, a competitive antagonists of the NMDA receptor on the analgesic actions of [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2, Glu4] deltorphin II (deltorphin II), the putative delta 1- and delta 2-opioid receptor agonists, respectively, were determined in the male Swiss-Webster mice. 2. Intracerebroventricular administration of DPDPE or deltorphin II produced analgesia. MK-801 administered intraperitoneally 10 min before the injection of DPDPE or deltorphin II, dose-dependently antagonized the analgesic actions of both drugs. 3. LY 235959 also dose-dependently antagonized the analgesic actions of DPDPE and deltorphin II. 4. The effects of MK-801 and LY 235959 on the binding of [3H]-DPDPE to mouse brain membranes were also determined. Neither of the NMDA receptor antagonists had any effect on the binding of [3H]-DPDPE. 5. It is concluded that competitive and noncompetitive antagonists of the NMDA receptor antagonize the analgesic action of delta 1- and delta 2-opioid receptor agonists and that such effects are not mediated via a direct interaction with brain delta-opioid receptors.
Bharagava
H N
HN
Department of Pharmaceutics and Pharmacodynamics, University of Illinois at Chicago 60612, USA.
Zhao
G M
GM
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017465:Receptors, Opioid, delta / Q000819:agonists*
D000701:Analgesics, Opioid; D000978:Antiparkinson Agents; D004745:Enkephalins; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D009842:Oligopeptides; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D016291:Dizocilpine Maleate; D020881:Enkephalin, D-Penicillamine (2,5)-; C088643:LY 235959