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
Pharmacological preconditioning of the brain: a possible interplay between opioid and calcitonin gene related peptide transduction systems.
The present study has been undertaken to investigate the possible link between calcitonin gene related peptide (CGRP) and opioid receptor transduction systems in the neuroprotective mechanism of pharmacological precondit...
Insulin suppresses the expression and function of breast cancer resistance protein in primary cultures of rat brain microvessel endothelial cells.
The aim of this study was to investigate the role of insulin in the regulation of breast cancer resistance protein (BCRP) function and expression using primary cultured rat brain microvessel endothelial cells (rBMECs) as...
Vascular prostaglandin synthesis: the early days.
Prostacyclin (PGI(2)) and thromboxane (TxA(2)) labile cyclooxygenase (COX) products via PGH(2) were identified in biological fluids by the ingenious application of the principle of parallel pharmacological assays develop...
Activity of essential phospholipids (EPL) from soybean in liver diseases.
Essential phospholipids (EPL) contain a highly purified extract of polyenylphosphatidylcholine (PPC) molecules from soybean. The main active ingredient is 1,2-dilinoleoylphosphatidylcholine (DLPC), which differentiates i...
Effect of pentoxifylline on hepatic injury caused in the rat by the administration of carbon tetrachloride or acetaminophen.
The effect of pentoxifylline (PTX) on acute liver injury caused by CCl(4) or acetaminophen was studied in the rat. PTX was given twice daily (18, 36 or 72 mg/kg), intraperitoneally (ip) for 5 days prior to CCl(4) or acet...