Synergistic interaction of pregabalin with the synthetic cannabinoid WIN 55,212-2 mesylate in the hot-plate test in mice: an isobolographic analysis.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 3
Abstract
Background: The aim of the study was to determine the type of interaction between pregabalin (a 3(rd)-generation antiepileptic drug) and WIN 55,212-2 mesylate (WIN - a highly potent non-selective cannabinoid CB1 and CB2 receptor agonist) administered in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice. 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.
Authors and Affiliations
Jarogniew Łuszczki, Magdalena Florek-Łuszczki
Keywords
Related Articles
- EP ID EP140540
- DOI -
- Views 88
- Downloads 0
C3435T Polymorphism of the ABCB1/MDR1 gene encoding P-glycoprotein in patients with inflammatory bowel disease in a Polish population.
Background: Inflammatory bowel disease (IBD) belongs to the group of chronic diseases of the gastrointestinal tract, prevalence of which is increasing in the Polish population. The two main clinical types of IBD are ulce...
Chronic exercise increases sensitivity to the conditioned rewarding effects of cocaine.
The purpose of this study was to determine whether chronic exercise alters sensitivity to the conditioned rewarding effects of cocaine. Female rats were obtained at weaning and randomly assigned to either sedentary or ex...
Influence of DRD2 and ANKK1 polymorphisms on the manifestation of withdrawal syndrome symptoms in alcohol addiction.
Background: We investigated the relationship between withdrawal syndrome symptoms and dopamine receptor 2 DRD2 gene polymorphisms-141 C I/D (rs1799732) exon 8 G/A (rs6276) and ANKK1 (Ankyrin Repeat and Kinase Domain Cont...
Influence of simvastatin at high dose and nifedipine on hemodynamic parameters in rabbits.
Recent findings in vitro have shown that statins could reduce cardiomyocyte viability. The correlation between statin cardiotoxicity, assessed in vitro, and cardiac efficiency, investigated in vivo has not been estimated...
Ejaculatory dysfunction in streptozotocin-induced diabetic rats: the role of testosterone.
Hyperglycemic and hypoinsulinemic states caused by diabetes mellitus are usually related to some type of sexual dysfunction, resulting in infertility in humans and experimental models, mostly due to their effects on ejac...