Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: an isobolographic analysis.
Journal Title: Pharmacological Reports - Year 2009, Vol 61, Issue 3
Abstract
This study was aimed at determining the analgesic effect of gabapentin and tiagabine, two antiepileptic drugs that were administered alone and in combination at a fixed ratio of 1:1, in the acute thermal pain model (hot-plate test) in mice. Linear regression analysis was used to evaluate the dose-response relationships between logarithms of antiepileptic drug doses and their resultant maximum possible antinociceptive effects in the mouse hot-plate test. From linear equations, we calculated doses that increased the antinociceptive effect by 50% (ED(50) values) for gabapentin, tiagabine and their combination. The type of interaction between gabapentin and tiagabine was assessed using the isobolographic analysis. Results indicated that both antiepileptic drugs produced the definite antinociceptive effect, and the experimentally derived ED(50) values for gabapentin and tiagabine, when applied alone, were 504.4 mg/kg and 5.67 mg/kg, respectively. With isobolography, the experimentally derived ED(50 mix) value for the fixed ratio combination of 1:1 was 139.31 mg/kg and significantly differed from the theoretically calculated ED(50 add) value, which was 255.04 mg/kg (p < 0.05), indicating the synergistic interaction between gabapentin and tiagabine in the hot-plate test in mice. In conclusion, the combination of tiagabine with gabapentin at a fixed ratio of 1:1 exerted a synergistic interaction in the mouse model of nociceptive pain. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial for pain relief in humans.
Authors and Affiliations
Jarogniew Luszczki, Agnieszka Kołacz, Ewa Wojda, Mirosław Czuczwar, Krzysztof Przesmycki, Stanisław Czuczwar
Keywords
Related Articles
- EP ID EP154952
- DOI -
- Views 101
- Downloads 0
Abstracts of the Third Conference on PROGRESS IN EPILEPTIC AND ANTIEPILETIC DRUGS.
Gap junctions synchronize vascular tone within the microcirculation.
Gap junctions are formed in the cardiovascular system by connexin40 (Cx40), Cx37, Cx43, and Cx45. These low resistance channels allow the transfer of ions and small molecules between cells. The longitudinal coupling of e...
Antiarrhythmic effect of prolonged morphine exposure is accompanied by altered myocardial adenylyl cyclase signaling in rats.
Background: Morphine is often administered to patients for pain management, but it is also recommended to ameliorate some types of cardiovascular diseases. Nevertheless, there is a lack of information regarding the effec...
Involvement of PI3-K in neuroprotective effects of the 1,25-dihydroxyvitamin D(3) analogue - PRI-2191.
The active form of 1,25-dihydroxyvitamin D(3) prevents neuronal damage in vitro and in vivo , however, it induces also hypercalcemia and hyperphosphatemia. Side-chain-modified analogues of 1,25-dihydroxyvitamin D(3), whi...
Neuraminidase inhibitors reduce nitric oxide production in influenza virus-infected and gamma interferon-activated RAW 264.7 macrophages.
The influenza virus (influenza) infection causes an intense infiltration of pulmonary tissues by macrophages, which abundantly generate a free radical, nitric oxide (NO) resulting in lung damage. Neuraminidase inhibitors...