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  • Title: Influence of idazoxan on analgesia, tolerance, and physical dependence of morphine in mice and rats in vivo.
    Author: Su RB, Li J, Gao K, Pei G, Qin BY.
    Journal: Acta Pharmacol Sin; 2000 Nov; 21(11):1011-5. PubMed ID: 11501055.
    Abstract:
    AIM: To study the influence of idazoxan (Ida), an antagonist of imidazoline receptors (I-R), on analgesia, tolerance, and physical dependence of morphine. METHODS: The effects of Ida on pain threshold and morphine analgesia were observed in mouse acetic acid writhing test and 55 degrees C hot plate test. The effect of Ida on morphine tolerance and physical dependence were observed in mouse tolerant model and in mice and rat models. RESULTS: Ida (3-9 mg/kg) significantly decreased the pain threshold by 120% in acetic acid writhing test and by 39% in 55 degrees C hot plate test of mice, respectively. It inhibited the analgesic effect of morphine in a dose-dependent manner. Ida promoted the development of tolerance to morphine in mice and induced the abstinence syndrome in morphine-dependent mice and rats similar to naloxone. CONCLUSION: I-R and its endogenous ligand agmatine might participate in the pain threshold and influence morphine analgesia as well as negatively regulate tolerance to and physical dependence on morphine.
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