Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: C57BL/6 mice underwent the chronic constriction injury (CCI) model of neuropathic pain. Mechanical and cold allodynia, plus cannabinoid side effects, were assessed in response to systemic drug application. KEY RESULTS:
JZL195 and the cannabinoid receptor agonist WIN55212 produced dose-dependent reductions in CCI-induced mechanical and cold allodynia, plus side effects including motor incoordination, catalepsy and sedation. JZL195 reduced allodynia with an ED50 at least four times less than that at which it produced side effects. By contrast, WIN55212 reduced allodynia and produce side effects with similar ED50s. The maximal anti-allodynic effect of JZL195 was greater than that produced by selective FAAH, or MAGL inhibitors. The JZL195-induced anti- allodynia was maintained during repeated treatment. CONCLUSIONS AND IMPLICATIONS:
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Authors | Nicholas S Adamson Barnes, Vanessa A Mitchell, Nicholas P Kazantzis, Christopher W Vaughan |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 173
Issue 1
Pg. 77-87
(Jan 2016)
ISSN: 1476-5381 [Electronic] England |
PMID | 26398331
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 The British Pharmacological Society. |
Chemical References |
- Benzamides
- Benzodioxoles
- Benzoxazines
- Carbamates
- JZL 184
- JZL195
- Morpholines
- Naphthalenes
- Piperazines
- Piperidines
- cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
- Monoacylglycerol Lipases
- Amidohydrolases
- fatty-acid amide hydrolase
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Topics |
- Amidohydrolases
(antagonists & inhibitors)
- Animals
- Benzamides
(pharmacology, therapeutic use)
- Benzodioxoles
(pharmacology, therapeutic use)
- Benzoxazines
(adverse effects, pharmacology, therapeutic use)
- Carbamates
(adverse effects, pharmacology, therapeutic use)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Hyperalgesia
(drug therapy)
- Male
- Mice
- Monoacylglycerol Lipases
(antagonists & inhibitors)
- Morpholines
(adverse effects, pharmacology, therapeutic use)
- Naphthalenes
(adverse effects, pharmacology, therapeutic use)
- Neuralgia
(drug therapy)
- Piperazines
(adverse effects, pharmacology, therapeutic use)
- Piperidines
(pharmacology, therapeutic use)
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