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  • 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.
    Author: Bhargava HN.
    Journal: Gen Pharmacol; 1995 Sep; 26(5):1055-60. PubMed ID: 7557250.
    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.
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