Justin N Siemian1, Jiuzhou Li2, Yanan Zhang3, Jun-Xu Li4. 1. Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, USA. 2. Department of Neurosurgery, Binzhou People's Hospital, Binzhou, Shandong Province, China. 3. Research Triangle Institute, Research Triangle Park, North Carolina, USA. 4. Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY, USA. junxuli@buffalo.edu.
Abstract
RATIONALE: Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for the justification of alternative pain therapies. OBJECTIVE: This study systematically examined the antihyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. METHODS: Von Frey and Hargreaves tests were used to examine the antihyperalgesic effects of drugs in complete Freund's adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. RESULTS: 2-BFI (3.2-17.8 mg/kg, i.p.), phenyzoline (17.8-100 mg/kg, i.p.), and acetaminophen (56-178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. CONCLUSIONS: Quantitative analysis of the antihyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen.
RATIONALE: Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for the justification of alternative pain therapies. OBJECTIVE: This study systematically examined the antihyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. METHODS:Von Frey and Hargreaves tests were used to examine the antihyperalgesic effects of drugs in complete Freund's adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. RESULTS:2-BFI (3.2-17.8 mg/kg, i.p.), phenyzoline (17.8-100 mg/kg, i.p.), and acetaminophen (56-178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. CONCLUSIONS: Quantitative analysis of the antihyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen.
Authors: Matthew Daubresse; Hsien-Yen Chang; Yuping Yu; Shilpa Viswanathan; Nilay D Shah; Randall S Stafford; Stefan P Kruszewski; G Caleb Alexander Journal: Med Care Date: 2013-10 Impact factor: 2.983
Authors: Linda Engström Ruud; Daniel Björk Wilhelms; Anna Eskilsson; Ana Maria Vasilache; Louise Elander; David Engblom; Anders Blomqvist Journal: Neuropharmacology Date: 2013-03-29 Impact factor: 5.250