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Isobolographic Analyses of Proglumide–Celecoxib Interaction in Rats with Painful Diabetic Neuropathy
Author(s) -
SuarezMendez Samuel,
TovillaZarate Carlos A.,
OrtegaVarela Luis F.,
BermudezOcaña Deysi Y.,
BléCastillo Jorge L.,
GonzálezCastro Thelma B.,
ZetinaEsquivel Alma M.,
DiazZagoya Juan C.,
Esther JuárezRojop Isela
Publication year - 2017
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.21382
Subject(s) - celecoxib , proglumide , pharmacology , hyperalgesia , medicine , antagonist , neuropathic pain , streptozotocin , diabetic neuropathy , nociception , diabetes mellitus , cholecystokinin receptor , endocrinology , receptor
Preclinical ResearchThe aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non‐selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase‐2 inhibitor, celecoxib in streptozotocin (STZ)‐induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0.5:0.5). Proglumide (20–160 mg/kg) and celecoxib (0.3–30 mg/kg) in these fixed dose ratio combinations induced dose‐dependent antihyperalgesia and an antiallodynic effect in diabetic rats. ED 40 values were calculated for the treatments and an isobologram was constructed. Theoretical ED 40 values for combination proglumide–celecoxib estimated from the isobolograms for antihyperalgesic and antiallodynic activity (30.50 ± 1.90 mg/kg and 45.81 ± 4.55 mg/kg, respectively) were obtained, while experimental ED 40 values for this antihyperalgesic and antiallodynic combined effect (13.83 ± 0.65 mg/kg and 17.74 ± 3.57 mg/kg; respectively) were significantly different. Coadministration of proglumide–celecoxib showed an interaction index value of 0.45 ± 0.03 for the antihyperalgesic effect and 0.39 ± 0.08 for the antiallodynic activity, indicating a synergistic interaction. These data suggest that proglumide and celecoxib can interact synergistically to reduce hyperalgesic and allodynic behaviors in diabetic neuropathy. This combination could be useful to treat neuropathic pain in diabetic patients. Drug Dev Res 78 : 116–123, 2017. ©2017 Wiley Periodicals, Inc.