title: Non-competitive antagonism of N-methyl-D-aspartate receptor inhibits tolerance to the analgesic action of U-50,488H, a kappa-opiate receptor agonist in the rat.
abstract: 1. The effect of dizocilpine (MK-801), a non-competitive inhibitor of N-methyl-D-aspartate (NMDA) receptor on the development of tolerance to the analgesic and hypothermic actions of U-50,488H, a highly selective kappa-opiate receptor agonist, was determined in the rat. 2. Male Sprague-Dawley rats were made tolerant to the pharmacological actions of U-50,488H by twice daily intraperitoneal (i.p.) injections of the drug (25 mg/kg) for 4 days. 3. Multiple injections of U-50,488H resulted in the development of tolerance to its analgesic and hypothermic actions in the rat. MK-801 injected 10 min before each injection of U-50,488H, dose-dependently inhibited the development of tolerance to the analgesic action but the tolerance to the hypothermic action of U-50,488H was unaffected. 4. Multiple injections of U-50,488H decreased the body weight gain. MK-801 dose-dependently decreased the gain in body weight further. 5. The results indicate that non-competitive antagonism of the NMDA receptor by MK-801 can selectively inhibit the tolerance to the analgesic action of U-50,488H in the rat, however, such an effect was associated with significant decreases in normal gain in body weight.
authors.affiliation: Department of Pharmaceutics and Pharmacodynamics (M/C 865), University of Illinois at Chicago 60612, USA.
authors.forename: H N
authors.initials: HN
authors.lastname: Bhargava
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013997:Time Factors
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D016291:Dizocilpine Maleate