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Modulation of opioids via protection of anandamide degradation by fatty acid amide hydrolase.
Eur J Pharmacol. 2008 Dec 14; 600(1-3):50-8.EJ

Abstract

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 CB(1) receptor antagonist, SR141716A (rimonabant), the kappa opioid receptor-selective antagonist, nor-Binaltorphimine (10 microg 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 CB(2) receptor antagonist, SR144528. In addition, nor-BNI (10 microg i.t) administration to FAAH(-/-) knockout mice produced a nociceptive response. The URB597/anandamide combination was not active in the CB(1)(-/-) 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 ED(50)=4.6 mg/kg [3.7-5.6] versus morphine/URB597/anandamide (ED(50)=2.5 mg/kg [1.9-3.4]). These data are the first demonstration that anandamide, if protected from degradation, acts via the CB(1) receptor to interact with kappa opioid receptor systems in opioid analgesia.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-00524, United States. vhaller@vcu.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18762181

Citation

Haller, Victoria L., et al. "Modulation of Opioids Via Protection of Anandamide Degradation By Fatty Acid Amide Hydrolase." European Journal of Pharmacology, vol. 600, no. 1-3, 2008, pp. 50-8.
Haller VL, Stevens DL, Welch SP. Modulation of opioids via protection of anandamide degradation by fatty acid amide hydrolase. Eur J Pharmacol. 2008;600(1-3):50-8.
Haller, V. L., Stevens, D. L., & Welch, S. P. (2008). Modulation of opioids via protection of anandamide degradation by fatty acid amide hydrolase. European Journal of Pharmacology, 600(1-3), 50-8. https://doi.org/10.1016/j.ejphar.2008.08.005
Haller VL, Stevens DL, Welch SP. Modulation of Opioids Via Protection of Anandamide Degradation By Fatty Acid Amide Hydrolase. Eur J Pharmacol. 2008 Dec 14;600(1-3):50-8. PubMed PMID: 18762181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of opioids via protection of anandamide degradation by fatty acid amide hydrolase. AU - Haller,Victoria L, AU - Stevens,David L, AU - Welch,Sandra P, Y1 - 2008/08/20/ PY - 2008/03/12/received PY - 2008/07/29/revised PY - 2008/08/08/accepted PY - 2008/9/3/pubmed PY - 2009/3/28/medline PY - 2008/9/3/entrez SP - 50 EP - 8 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 600 IS - 1-3 N2 - 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 CB(1) receptor antagonist, SR141716A (rimonabant), the kappa opioid receptor-selective antagonist, nor-Binaltorphimine (10 microg 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 CB(2) receptor antagonist, SR144528. In addition, nor-BNI (10 microg i.t) administration to FAAH(-/-) knockout mice produced a nociceptive response. The URB597/anandamide combination was not active in the CB(1)(-/-) 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 ED(50)=4.6 mg/kg [3.7-5.6] versus morphine/URB597/anandamide (ED(50)=2.5 mg/kg [1.9-3.4]). These data are the first demonstration that anandamide, if protected from degradation, acts via the CB(1) receptor to interact with kappa opioid receptor systems in opioid analgesia. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/18762181/Modulation_of_opioids_via_protection_of_anandamide_degradation_by_fatty_acid_amide_hydrolase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00874-1 DB - PRIME DP - Unbound Medicine ER -