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Effects of URB597 as an inhibitor of fatty acid amide hydrolase on modulation of nociception in a rat model of cholestasis.
Eur J Pharmacol. 2008 Sep 04; 591(1-3):132-5.EJ

Abstract

Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. The use of inhibitors of endocannabinoid metabolism is a novel means of pharmacologically increasing endocannabinoid levels. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effects of URB597, a selective inhibitor of FAAH (fatty acid amide hydrolase), on modulation of nociception in a model of elevated endogenous opioid tone, cholestasis. Cholestasis was induced by ligation of the main bile duct using two ligatures and then transection of the duct at the midpoint between them. Seven days after surgery, tail-flick latencies were measured at 60 min after drug administration. A significant increase (P<0.001) in nociception threshold was observed in cholestatic rats compared to unoperated and sham groups. Administration of URB597 (0.3 mg/kg, i.p.) in cholestatic animals significantly (P<0.001) increased tail-flick latency compared to the vehicle treated cholestatic group. URB597 injection to unoperated and sham groups caused a significant (P<0.05, P<0.05) increase in tail-flick latency compared to their respective vehicle treated groups. The antinociceptive effect of URB597 was blocked by coadministration of a cannabinoid CB(1) receptor antagonist, AM251 (1 mg/kg, i.p.) but not by a cannabinoid CB(2) receptor antagonist, SR144528 (1 mg/kg, i.p.) with URB597. These data showed that URB597 as a FAAH inhibitor potentiates antinociception induced by cholestasis in tail-flick test and that the inhibitory effects of URB597 in this model are mediated by cannabinoid CB(1) and not CB(2) receptors.

Authors+Show Affiliations

Department of Biology, School of Basic Sciences, Bu-Ali Sina University, Hamadan, Iran. p.hasanein@basu.ac.irNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18593578

Citation

Hasanein, Parisa, et al. "Effects of URB597 as an Inhibitor of Fatty Acid Amide Hydrolase On Modulation of Nociception in a Rat Model of Cholestasis." European Journal of Pharmacology, vol. 591, no. 1-3, 2008, pp. 132-5.
Hasanein P, Shahidi S, Komaki A, et al. Effects of URB597 as an inhibitor of fatty acid amide hydrolase on modulation of nociception in a rat model of cholestasis. Eur J Pharmacol. 2008;591(1-3):132-5.
Hasanein, P., Shahidi, S., Komaki, A., & Mirazi, N. (2008). Effects of URB597 as an inhibitor of fatty acid amide hydrolase on modulation of nociception in a rat model of cholestasis. European Journal of Pharmacology, 591(1-3), 132-5. https://doi.org/10.1016/j.ejphar.2008.06.061
Hasanein P, et al. Effects of URB597 as an Inhibitor of Fatty Acid Amide Hydrolase On Modulation of Nociception in a Rat Model of Cholestasis. Eur J Pharmacol. 2008 Sep 4;591(1-3):132-5. PubMed PMID: 18593578.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of URB597 as an inhibitor of fatty acid amide hydrolase on modulation of nociception in a rat model of cholestasis. AU - Hasanein,Parisa, AU - Shahidi,Siamak, AU - Komaki,Alireza, AU - Mirazi,Naser, Y1 - 2008/06/19/ PY - 2008/02/18/received PY - 2008/06/06/revised PY - 2008/06/12/accepted PY - 2008/7/3/pubmed PY - 2008/10/16/medline PY - 2008/7/3/entrez SP - 132 EP - 5 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 591 IS - 1-3 N2 - Cholestasis is associated with increased activity of the endogenous opioid system that results in analgesia. Endocannabinoid system can reduce pain sensitivity. The use of inhibitors of endocannabinoid metabolism is a novel means of pharmacologically increasing endocannabinoid levels. Considering the interaction that has been shown between the endogenous opioid and endocannabinoid systems in nociception processing, we studied the effects of URB597, a selective inhibitor of FAAH (fatty acid amide hydrolase), on modulation of nociception in a model of elevated endogenous opioid tone, cholestasis. Cholestasis was induced by ligation of the main bile duct using two ligatures and then transection of the duct at the midpoint between them. Seven days after surgery, tail-flick latencies were measured at 60 min after drug administration. A significant increase (P<0.001) in nociception threshold was observed in cholestatic rats compared to unoperated and sham groups. Administration of URB597 (0.3 mg/kg, i.p.) in cholestatic animals significantly (P<0.001) increased tail-flick latency compared to the vehicle treated cholestatic group. URB597 injection to unoperated and sham groups caused a significant (P<0.05, P<0.05) increase in tail-flick latency compared to their respective vehicle treated groups. The antinociceptive effect of URB597 was blocked by coadministration of a cannabinoid CB(1) receptor antagonist, AM251 (1 mg/kg, i.p.) but not by a cannabinoid CB(2) receptor antagonist, SR144528 (1 mg/kg, i.p.) with URB597. These data showed that URB597 as a FAAH inhibitor potentiates antinociception induced by cholestasis in tail-flick test and that the inhibitory effects of URB597 in this model are mediated by cannabinoid CB(1) and not CB(2) receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/18593578/Effects_of_URB597_as_an_inhibitor_of_fatty_acid_amide_hydrolase_on_modulation_of_nociception_in_a_rat_model_of_cholestasis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(08)00675-4 DB - PRIME DP - Unbound Medicine ER -