Abstract | BACKGROUND: METHODS: Linear regression analysis was used to evaluate the dose-response relationships between logarithms of drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, doses were calculated that increased the antinociceptive effect by 30% (ED(30) values) for pregabalin, WIN, and their combination. The type of interaction between pregabalin and WIN was assessed using the isobolographic analysis. RESULTS: Results indicated that both compounds produced a definite antinociceptive effect, and the experimentally-derived ED(30) values for pregabalin and WIN, when applied alone, were 29.4 mg/kg and 10.5 mg/kg, respectively. With isobolography, the experimentally derived ED(30 mix) value for the fixed ratio combination of 1:1 was 5.7 mg/kg, and differed significantly from the theoretically calculated ED(30 add) value of 19.95 mg/kg (p < 0.01), indicating synergistic interaction between pregabalin and WIN in the hot-plate test in mice. CONCLUSIONS: Isobolographic analysis demonstrated that the combination of WIN with pregabalin at a fixed ratio of 1:1 exerted synergistic interaction in the mouse model of acute thermal pain. If the results from this study could be adapted to clinical settings, the combination of WIN with pregabalin might be beneficial for pain relief in humans.
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Authors | Jarogniew J Luszczki, Magdalena Florek-Łuszczki |
Journal | Pharmacological reports : PR
(Pharmacol Rep)
Vol. 64
Issue 3
Pg. 723-32
( 2012)
ISSN: 2299-5684 [Electronic] Switzerland |
PMID | 22814025
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics
- Benzoxazines
- Morpholines
- Naphthalenes
- Receptor, Cannabinoid, CB1
- Receptor, Cannabinoid, CB2
- Pregabalin
- gamma-Aminobutyric Acid
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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Topics |
- Acute Pain
(drug therapy, physiopathology)
- Analgesics
(administration & dosage, pharmacology)
- Animals
- Benzoxazines
(administration & dosage, pharmacology)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Synergism
- Linear Models
- Male
- Mice
- Morpholines
(administration & dosage, pharmacology)
- Naphthalenes
(administration & dosage, pharmacology)
- Pregabalin
- Receptor, Cannabinoid, CB1
(agonists)
- Receptor, Cannabinoid, CB2
(agonists)
- gamma-Aminobutyric Acid
(administration & dosage, analogs & derivatives, pharmacology)
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