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Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models.
Clin Exp Pharmacol Physiol. 2007 Nov; 34(11):1186-90.CE

Abstract

1. Although cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central cannabinoid CB(1) receptor-mediated motor and psychotropic side-effects. The actions of endocannabinoids, such as anandamide, are terminated by uptake and subsequent intracellular enzymatic degradation. In the present study, we examined the effect of acute administration of the anandamide transport inhibitor AM404 in rat models of chronic neuropathic and inflammatory pain. 2. Systemic administration of AM404 (10 mg/kg) reduced mechanical allodynia in the partial sciatic nerve ligation (PNL) model of neuropathic pain, but not in the complete Freund's adjuvant (CFA) model of inflammatory pain. 3. The effect of AM404 in the PNL model was abolished by coapplication with the selective cannabinoid CB(1) receptor antagonist AM251 (1 mg/kg). AM404 did not produce a reduction in motor performance in either the PNL or CFA models. 4. These findings suggest that acute administration of AM404 reduces allodynia in a neuropathic pain model via cannabinoid CB(1) receptor activation, without causing the undesirable motor disruption associated with cannabinoid receptor agonists.

Authors+Show Affiliations

Pain Management Research Institute, Kolling Institute, Northern Clinical School, The University of Sydney, St Leonards, New South Wales, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17880375

Citation

Mitchell, Vanessa A., et al. "Actions of the Endocannabinoid Transport Inhibitor AM404 in Neuropathic and Inflammatory Pain Models." Clinical and Experimental Pharmacology & Physiology, vol. 34, no. 11, 2007, pp. 1186-90.
Mitchell VA, Greenwood R, Jayamanne A, et al. Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models. Clin Exp Pharmacol Physiol. 2007;34(11):1186-90.
Mitchell, V. A., Greenwood, R., Jayamanne, A., & Vaughan, C. W. (2007). Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models. Clinical and Experimental Pharmacology & Physiology, 34(11), 1186-90.
Mitchell VA, et al. Actions of the Endocannabinoid Transport Inhibitor AM404 in Neuropathic and Inflammatory Pain Models. Clin Exp Pharmacol Physiol. 2007;34(11):1186-90. PubMed PMID: 17880375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Actions of the endocannabinoid transport inhibitor AM404 in neuropathic and inflammatory pain models. AU - Mitchell,Vanessa A, AU - Greenwood,Ruth, AU - Jayamanne,Angelo, AU - Vaughan,Christopher W, PY - 2007/9/21/pubmed PY - 2007/12/6/medline PY - 2007/9/21/entrez SP - 1186 EP - 90 JF - Clinical and experimental pharmacology & physiology JO - Clin. Exp. Pharmacol. Physiol. VL - 34 IS - 11 N2 - 1. Although cannabinoid receptor agonists have analgesic activity in chronic pain states, they produce a spectrum of central cannabinoid CB(1) receptor-mediated motor and psychotropic side-effects. The actions of endocannabinoids, such as anandamide, are terminated by uptake and subsequent intracellular enzymatic degradation. In the present study, we examined the effect of acute administration of the anandamide transport inhibitor AM404 in rat models of chronic neuropathic and inflammatory pain. 2. Systemic administration of AM404 (10 mg/kg) reduced mechanical allodynia in the partial sciatic nerve ligation (PNL) model of neuropathic pain, but not in the complete Freund's adjuvant (CFA) model of inflammatory pain. 3. The effect of AM404 in the PNL model was abolished by coapplication with the selective cannabinoid CB(1) receptor antagonist AM251 (1 mg/kg). AM404 did not produce a reduction in motor performance in either the PNL or CFA models. 4. These findings suggest that acute administration of AM404 reduces allodynia in a neuropathic pain model via cannabinoid CB(1) receptor activation, without causing the undesirable motor disruption associated with cannabinoid receptor agonists. SN - 0305-1870 UR - https://www.unboundmedicine.com/medline/citation/17880375/Actions_of_the_endocannabinoid_transport_inhibitor_AM404_in_neuropathic_and_inflammatory_pain_models_ L2 - https://doi.org/10.1111/j.1440-1681.2007.04692.x DB - PRIME DP - Unbound Medicine ER -