Dataset Information

MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models.

ABSTRACT: BACKGROUND AND PURPOSE: There is growing interest in using cannabinoid type 2 (CB(2)) receptor agonists for the treatment of neuropathic pain. In this report, we describe the pharmacological characteristics of MDA7 (1-[(3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl]piperidine), a novel CB(2) receptor agonist. EXPERIMENTAL APPROACH: We characterized the pharmacological profile of MDA7 by using radioligand-binding assays and in vitro functional assays at human cannabinoid type 1 (CB(1)) and CB(2) receptors. In vitro functional assays were performed at rat CB(1) and CB(2) receptors. The effects of MDA7 in reversing neuropathic pain were assessed in spinal nerve ligation and paclitaxel-induced neuropathy models in rats. KEY RESULTS: MDA7 exhibited selectivity and agonist affinity at human and rat CB(2) receptors. MDA7 treatment attenuated tactile allodynia produced by spinal nerve ligation or by paclitaxel in a dose-related manner. These effects were selectively antagonized by a CB(2) receptor antagonist but not by CB(1) or opioid receptor antagonists. MDA7 did not affect rat locomotor activity. CONCLUSION AND IMPLICATIONS: MDA7, a novel selective CB(2) agonist, was effective in suppressing neuropathic nociception in two rat models without affecting locomotor behaviour. These results confirm the potential for CB(2) agonists in the treatment of neuropathic pain.

SUBMITTER: Naguib M

PROVIDER: S-EPMC2597252 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models.

Naguib M M Diaz P P Xu J J JJ Astruc-Diaz F F Craig S S Vivas-Mejia P P Brown D L DL

British journal of pharmacology 20080901 7

<h4>Background and purpose</h4>There is growing interest in using cannabinoid type 2 (CB(2)) receptor agonists for the treatment of neuropathic pain. In this report, we describe the pharmacological characteristics of MDA7 (1-[(3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl)carbonyl]piperidine), a novel CB(2) receptor agonist.<h4>Experimental approach</h4>We characterized the pharmacological profile of MDA7 by using radioligand-binding assays and in vitro functional assays at human cannabinoid t ...[more]

PMID: 18846037

Similar Datasets

Project description:Background:Reactive oxygen species (ROS) induced oxidative stress is linked to numerous neurological diseases, including neuropathic pain. Natural ROS scavenging enzymes like superoxide dismutase (SOD) and catalase have been found to be efficient in alleviating neuropathic pain. However, their sensitivity towards extreme pH and a short half-life limit their efficacy in vivo. Manganese oxide nanoparticles (MONPs) are recently known to possess ROS scavenging properties. In this study, MONPs were examined for their therapeutic effect on neuropathic pain. Methods:The MONPs were synthesized by a hydrothermal method. The synthesized MONPs were characterized by UV/Vis, TEM, SEM, FTIR, NTA and XRD. The biocompatibility of the nanoparticles is evaluated in neural cells using LDH assay. MONPs were evaluated for their antioxidant activity by DPPH assay. In addition, in vitro ROS scavenging properties were examined in bone marrow-derived macrophage (BMDM) cells using 2',7'-dichlorofluorescin diacetate (DCFDA) assay. To evaluate the in vivo efficacy of nanoparticles, neuropathic pain was induced in Wistar rats by partial sciatic nerve transection (PSNT). On post-transection days 14 to 18, rats were intrathecally injected with MONPs and paw withdrawal threshold was measured. The spinal cords were collected and processed for Western blotting and histological analysis. Results:The synthesized MONPs were biocompatible and showed effective antioxidant activity against DPPH free radical scavenging. Further, the nanoparticles scavenged ROS efficiently in vitro in BMDM and their intrathecal administration significantly reduced mechanical allodynia as well as the expression of cyclooxygenase-2 (COX-2), an important mediator of chronic and inflammatory pain in the spinal dorsal horns of PSNT rats. Conclusion:As ROS play a significant role in neuropathic pain, we expect that MONPs could be a promising tool for the treatment of various inflammatory diseases and might also serve as a potential nanocarrier for the delivery of analgesics.

Dataset Information

MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models.

Publications

MDA7: a novel selective agonist for CB2 receptors that prevents allodynia in rat neuropathic pain models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets