Abstract | BACKGROUND: METHODS: Mouse models of pain, locomotor behavior, and coordination were used. Fenobam or vehicle (n = 8 or 11 per group) was administered for 14 days, and analgesic tolerance to fenobam was assessed using the formalin test. Histopathologic examination, hematology, and clinical chemistry analysis after 14-day fenobam administration were also assessed (n = 12 or 9). The effects of fenobam on locomotor activity were assessed in the open field and elevated zero maze (n = 8 or 7). Coordination was assessed using ledge crossing and vertical pole descent tasks (n = 11 or 10). RESULTS: Tolerance to fenobam's analgesic effect did not develop after 14 days. Chronic fenobam administration resulted in statistically significantly less weight gain compared with vehicle control subjects, but did not cause any physiologically or statistically significant hematologic abnormalities, altered organ function, or abnormal histopathology of the liver, brain, or testes. Fenobam administration resulted in a metabotropic glutamate receptor 5-dependent increase in exploratory behavior but does not impair motor coordination at analgesic doses. CONCLUSIONS:
Analgesic tolerance to repeat fenobam dosing does not develop. Chronic dosing of up to 14 days is well tolerated. Fenobam represents a promising candidate for the treatment of human pain conditions.
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Authors | Michael C Montana, Beth A Conrardy, Laura F Cavallone, Benedict J Kolber, Lesley K Rao, Suellen C Greco, Robert W Gereau 4th |
Journal | Anesthesiology
(Anesthesiology)
Vol. 115
Issue 6
Pg. 1239-50
(Dec 2011)
ISSN: 1528-1175 [Electronic] United States |
PMID | 22037639
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Analgesics
- Imidazoles
- Receptor, Metabotropic Glutamate 5
- Receptors, Metabotropic Glutamate
- fenobam
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Topics |
- Analgesics
(blood, pharmacology)
- Analysis of Variance
- Animals
- Behavior, Animal
(drug effects)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Tolerance
- Eating
(drug effects)
- Imidazoles
(blood, pharmacology)
- Male
- Mice
- Motor Activity
(drug effects)
- Pain
(drug therapy)
- Pain Measurement
- Receptor, Metabotropic Glutamate 5
- Receptors, Metabotropic Glutamate
(antagonists & inhibitors)
- Weight Gain
(drug effects)
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