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Enhancement of Antihyperalgesia by the Coadministration of N‐palmitoylethanolamide and Acetaminophen in Diabetic Rats
Author(s) -
DécigaCampos Myrna,
OrtízAndrade Rolffy
Publication year - 2015
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.21259
Subject(s) - palmitoylethanolamide , acetaminophen , pharmacology , ec50 , medicine , ed50 , chemistry , in vitro , agonist , biochemistry , receptor , cannabinoid receptor
Preclinical ResearchThe objective of this study was to evaluate the pharmacological antihyperalgesic interaction between N‐palmitoylethanolamide (PEA) and acetaminophen in diabetic rats using the formalin paw test. Streptozotocin (STZ)‐induced diabetic rats received subcutaneous injections in the paw of PEA alone (1–100 μg/paw) or acetaminophen alone (3–300 μg/paw) 15 min before formalin (0.5%) injection. The results revealed concentration‐dependent responses produced by PEA (EC 50 = 7.19 ± 0.7 μg/paw) and acetaminophen (EC 50 = 57.9 ± 1.9 μg/paw). Isobolographic analysis was used to evaluate the pharmacological interaction between the PEA + acetaminophen using the EC 50 value and a fixed 1:1 ratio combination. The isobologram demonstrated that the combination investigated in this study produced a synergistic interaction; the experimental value (EC 50 = 23.64 ± 1.9 μg/paw) was significantly smaller than those that resulted from theoretical calculations (EC 50 = 32.56 μg/paw). These results provide evidence that PEA in combination with acetaminophen could be useful for pain therapy in neuropathic diabetic patients. Drug Dev Res 76 : 228–234, 2015. © 2015 Wiley Periodicals, Inc.