Abstract | OBJECTIVE: DESIGN: RESULTS: The maximum nonsedating doses were: morphine, 3.2 mg/kg; CNSB002 10.0 mg/kg; 5.0 mg/kg CNSB002 with morphine 3.2 mg/kg in combination. The doses calculated to cause 50% reversal of hyperalgesia (ED50) were 7.54 (1.81) and 4.83 (1.54) in the carrageenan model and 44.18 (1.37) and 9.14 (1.24) in the STZ-induced neuropathy model for CNSB002 and morphine, respectively (mg/kg; mean, SEM). These values were greater than the maximum nonsedating doses. The ED50 values for morphine when given in combination with CNSB002 (5 mg/kg) were less than the maximum nonsedating dose: 0.56 (1.55) in the carrageenan model and 1.37 (1.23) in the neuropathy model (mg/kg; mean, SEM). The antinociception after morphine (3.2 mg/kg) was increased by co-administration with CNSB002 from 28.0 and 31.7% to 114.6 and 56.9% reversal of hyperalgesia in the inflammatory and neuropathic models, respectively (P < 0.01; one-way analysis of variance-significantly greater than either drug given alone). CONCLUSIONS: The maximum antihyperalgesic effect achievable with nonsedating doses of morphine may be increased significantly when the drug is used in combination with CNSB002.
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Authors | Anton Kolosov, Colin S Goodchild, Ian Cooke |
Journal | Pain medicine (Malden, Mass.)
(Pain Med)
Vol. 11
Issue 1
Pg. 106-18
(Jan 2010)
ISSN: 1526-4637 [Electronic] England |
PMID | 20447294
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amines
- Analgesics, Opioid
- Cyclohexanecarboxylic Acids
- GABA Modulators
- Piperazines
- Sodium Channel Blockers
- AM 36
- gamma-Aminobutyric Acid
- Gabapentin
- Morphine
- Carrageenan
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Topics |
- Amines
(therapeutic use)
- Analgesics, Opioid
(administration & dosage, therapeutic use)
- Animals
- Carrageenan
- Cyclohexanecarboxylic Acids
(therapeutic use)
- Diabetes Mellitus, Experimental
(complications)
- Diabetic Nephropathies
(drug therapy)
- Dose-Response Relationship, Drug
- Drug Synergism
- GABA Modulators
(therapeutic use)
- Gabapentin
- Inflammation
(chemically induced, complications, drug therapy)
- Male
- Morphine
(administration & dosage, therapeutic use)
- Motor Activity
(drug effects)
- Pain
(drug therapy, etiology)
- Pain Measurement
- Peripheral Nervous System Diseases
(complications, drug therapy)
- Piperazines
(therapeutic use)
- Rats
- Rats, Wistar
- Sodium Channel Blockers
(therapeutic use)
- gamma-Aminobutyric Acid
(therapeutic use)
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