title: Combination of diacerhein and antiepileptic drugs after local peripheral, and oral administration in the rat formalin test.
abstract: Preclinical Research The 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 ED30 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 ED30 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.
authors.affiliation: Facultad de Químico-Farmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, 58240, Morelia, Michoacán, México.
authors.forename: Angel
authors.initials: A
authors.lastname: Zúñiga-Romero
authors.forename: Martha Karina
authors.initials: MK
authors.lastname: Ponce-Chávez
authors.forename: Marcia Yvette
authors.initials: MY
authors.lastname: Gauthereau-Torres
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Ortega-Varela
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000927:Anticonvulsants / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007279:Injections, Subcutaneous; D059226:Nociceptive Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D045442:Rotarod Performance Test
chemical_list: D000700:Analgesics; D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; C025292:diacerein
keywords: antiepileptics; antinociception; diacerhein; formalin test; isobolograms; synergy