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Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test
Author(s) -
ZúñigaRomero Angel,
PonceChávez Martha Karina,
GauthereauTorres Marcia Yvette,
OrtegaVarela Luis Fernando
Publication year - 2014
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21232
Subject(s) - topiramate , carbamazepine , gabapentin , pharmacology , anticonvulsant , nociception , oral administration , chemistry , medicine , epilepsy , receptor , biochemistry , alternative medicine , pathology , psychiatry
Preclinical ResearchThe present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin‐induced nociception. Diacerhein, each of the antiepileptics or a fixed dose‐ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose‐dependent antinociceptive effect when administered by both routes. Theoretical ED 30 values for the combination estimated from the isobolograms were obtained as follows: diacerhein‐carbamazepine (85.99 ± 7.07 μg/paw; 56.53 ± 4.56 mg/kg po), diacerhein‐topiramate (197.97 ± 22.90 μg/paw; 13.06 ± 2.44 mg/kg po) and diacerhein‐gabapentin (96.87 ± 17.73 μg/paw; 17.90 ± 4.70 mg/kg p.o.) for the local peripheral and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED 30 values: diacerhein‐carbamazepine (49.33 ± 3.37 μg/paw; 35.49 ± 7.91 mg/kg po), diacerhein‐topiramate (133.00 ± 39.10 μg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein‐gabapentin (70.98 ± 14.73 μg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile.