Pharmacology
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Numerous agents have been demonstrated to potentiate morphine analgesia, including clonidine (alpha(2)-adrenergic and I(1)-imidazoline receptor agonist) and BMS182874 (endothelin-A, ET(A,) receptor antagonist). ET has been shown to affect pharmacological actions of clonidine. The present study was conducted to determine whether alpha(2)-adrenergic and/or I(1)-imidazoline receptors are involved in the augmentation of morphine and oxycodone analgesia by clonidine and BMS182874. ⋯ This is the first report showing that clonidine and BMS182874 augment oxycodone analgesia. Results suggest that alpha(2)-adrenergic receptors are involved in clonidine-induced, but not in the BMS182874-induced, potentiation of the analgesic effects of morphine or oxycodone, and that I(1)-imidazoline receptors are involved in the potentiation of oxycodone analgesia, but not morphine analgesia, by clonidine and BMS182874.