کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2534571 | 1559096 | 2008 | 9 صفحه PDF | دانلود رایگان |
Lack of involvement of the opioid system with the endocannabinoid, arachidonylethanolamide (anandamide) was possibly due to hydrolysis by fatty acid amide hydrolase (FAAH). Cyclohexylcarbamic acid 3′-carbamoyl-biphenyl-3-yl ester (URB597) is an inhibitor of FAAH, increases brain anandamide levels and enhances anandamide-induced antinociception in male ICR mice (25–30 g). The combination of URB597 (10 mg/kg, i.p.) and anandamide (40 mg/kg, i.p.) produced maximal antinociception in the mouse tail-flick test [68.7 ± 16.8 percent maximum possible effect (%MPE)], versus either substance alone (27.3 ± 7.9%MPE and 4.6 ± 2.3%MPE, respectively) and is significantly blocked (p < 0.05) by the cannabinoid CB1 receptor antagonist, SR141716A (rimonabant), the kappa opioid receptor-selective antagonist, nor-Binaltorphimine (10 μg i.t.; 12.7 ± 4.0%MPE) and the mu opioid receptor antagonist, naloxone (1 mg/kg, s.c.; 6.0 ± 3.8%MPE), but not by the delta opioid receptor-selective antagonist, naltrindole (2 mg/kg, s.c.; 29.7 ± 8.2%MPE) or the cannabinoid CB2 receptor antagonist, SR144528. In addition, nor-BNI (10 μg i.t) administration to FAAH−/− knockout mice produced a nociceptive response. The URB597/anandamide combination was not active in the CB1−/− knockout mice, but retained activity in the MOR−/− knockout mice. The sub-active combination of (URB597 10 mg/kg, i.p/anandamide 10 mg/kg, i.p.; 15.5 ± 4.3%MPE) shifted the dose response curve of morphine to the left (morphine alone ED50 = 4.6 mg/kg [3.7–5.6] versus morphine/URB597/anandamide (ED50 = 2.5 mg/kg [1.9–3.4]). These data are the first demonstration that anandamide, if protected from degradation, acts via the CB1 receptor to interact with kappa opioid receptor systems in opioid analgesia.
Journal: European Journal of Pharmacology - Volume 600, Issues 1–3, 14 December 2008, Pages 50–58