Reference

Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain

All Rights Reserved. Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain. Jhaveri, Maulik D.; Richardson, Denise; Kendall, David A.; Barrett, David A.; Chapman, Victoria (School of Biomedical Sciences, Medical School, Queens Medical Centre, University of Nottingham, Nottinghamshire NG7 2UH, UK). Journal of Neuroscience, 26(51), 13318-13327 (English) 2006 Society for Neuroscience. CODEN: JNRSDS. ISSN: 0270-6474. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 4 Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to det. whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain. Electrophysiol. studies were performed 14-18 d after spinal nerve ligation or sham surgery, and the effects of the FAAH inhibitor cyclohexylcarbamic acid 3-carbamoyl biphenyl-3-yl ester (URB597) on mech. evoked responses of spinal neurons and levels of endocannabinoids were detd. Intraplantar URB597 (25 mg in 50 ml) significantly (p < 0.01) attenuated mech. evoked responses of spinal neurons in sham-operated rats. Effects of URB597 were blocked by the cannabinoid 1 receptor (CB1) antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H- pyrazole-3-carboxamide] (30 mg in 50 ml) and the opioid receptor antagonist naloxone. 546141-08-6 and 153301-19-0 which are cas registry numbers of chemicals are mentioned. URB597 treatment increased levels of anandamide, 2-arachidonyl glycerol, and oleoyl ethanolamide in the ipsilateral hindpaw of sham-operated rats. Intraplantar URB597 (25 mg in 50 ml) did not, however, alter mech. evoked responses of spinal neurons in spinal nerve ligated (SNL) rats or hindpaw levels of endocannabinoids. Intraplantar injection of a higher dose of URB597 (100 mg in 50 ml) significantly (p < 0.05) attenuated evoked responses of spinal neurons in SNL rats but did not alter hindpaw levels of endocannabinoids. Spinal administration of URB597 attenuated evoked responses of spinal neurons and elevated levels of endocannabinoids in sham-operated and SNL rats. These data suggest that peripheral FAAH activity may be altered or that alternative pathways of metab. have greater importance in SNL rats. .

Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat

All Rights Reserved. Effects of the FAAH inhibitor, URB597, and anandamide on lithium-induced taste reactivity responses: a measure of nausea in the rat. Cross-Mellor, Shelley K.; Ossenkopp, Klaus-Peter; Piomelli, Daniele; Parker, Linda A. (Department of Psychology, University of Guelph, Guelph, ON N1G 2W1, Can.). Psychopharmacology (Berlin, Germany), 190(2), 135-143 (English) 2007 Springer GmbH. CODEN: PSCHDL. ISSN: 0033-3158. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The endogenous cannabinoid system plays a vital role in the control of nausea and emesis. Because of the rapid breakdown and hydrolysis of endocannabinoids, such as anandamide, the therapeutic effects may be enhanced by prolonging their duration of action. The present expt. evaluated the potential of various doses of URB597, a fatty acid amide hydrolase (FAAH) inhibitor, alone and in combination with systemic administration of anandamide to modulate the establishment of lithium-induced conditioned taste reactivity responses in rats. In expt. 1, on the conditioning day, rats first received an injection of 0.3 mg/kg URB597, 0.15 mg/kg URB597, or vehicle and then received a second injection of anandamide (5 mg/kg) or vehicle, before a 3-min exposure of 0.1% saccharin by intraoral infusion. Immediately after the saccharin exposure, the rats were injected with lithium chloride. On each of three test days, rats received a 3-min intraoral infusion of saccharin soln., and the taste reactivity responses were videotaped and monitored. In expt. 2, the effects of pretreatment with the CB1 antagonist, AM-251, on URB597 and anandamide-induced suppressed aversion was evaluated.In this experiment, several chemicals are used like 94421-68-8 and 546141-08-6 Administration of URB597 alone and in combination with anandamide reduced active rejection reactions elicited by a LiCl-paired saccharin soln.; both effects were reversed by pretreatment with AM-251, suggesting that they were CB1 receptor mediated. The results suggest that prolonging the action of anandamide by pretreatment with the FAAH inhibitor, URB597, suppresses lithium-induced nausea in the rat. .