TY - JOUR
AU - Andurkar, Shridhar V.
AB - Background: Numerous agents have been demonstrated to potentiate morphine analgesia, including clonidine (α<sub>2</sub>-adrenergic and I<sub>1</sub>-imidazoline receptor agonist) and BMS182874 (endothelin-A, ET<sub>A,</sub> receptor antagonist). ET has been shown to affect pharmacological actions of clonidine. The present study was conducted to determine whether α<sub>2</sub>-adrenergic and/or I<sub>1</sub>-imidazoline receptors are involved in the augmentation of morphine and oxycodone analgesia by clonidine and BMS182874. Methods: Analgesic tail flick latencies were measured in rats at various time intervals, and were converted to AUC₀→<sub>360 min</sub>. Results: It was found that clonidine produced mild analgesia, while BMS182874 did not have any analgesic effect. Clonidine (p = 0.015) and BMS182874 (p = 0.009) enhanced the analgesic action of morphine and oxycodone. Clonidine- or BMS182874-induced increases in the analgesic effect of morphine were not inhibited by idazoxan (I<sub>1</sub>-imidazoline receptor antagonist), while increases in the analgesic effect of oxycodone were blocked by idazoxan. Yohimbine (α<sub>2</sub>-adrenergic receptor antagonist) blocked the clonidine-induced potentiation of analgesic effect of morphine (p = 0.036) and oxycodone (p = 0.0167), while yohimbine did not affect BMS182874-induced potentiation of the analgesic effect of morphine or oxycodone. Conclusions: This is the first report showing that clonidine and BMS182874 augment oxycodone analgesia. Results suggest that α<sub>2</sub>-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<sub>1</sub>-imidazoline receptors are involved in the potentiation of oxycodone analgesia, but not morphine analgesia, by clonidine and BMS182874.
TI - Determination of Adrenergic and Imidazoline Receptor Involvement in Augmentation of Morphine and Oxycodone Analgesia by Clonidine and BMS182874
JF - Pharmacology
DO - 10.1159/000178812
DA - 2008-01-01
UR - https://www.deepdyve.com/lp/karger/determination-of-adrenergic-and-imidazoline-receptor-involvement-in-MB9WXZ8DIs
SP - 45
EP - 58
VL - 83
IS - 1
DP - DeepDyve
ER -