Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding.
Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding.
复制标题
成年雄性大鼠中咪唑啉 I2 受体配体和对乙酰氨基酚之间的相互作用：镇痛和时间表控制反应。
DOI：
10.1007/s00213-015-4166-9
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发表时间：
2016-03
影响因子：
3.4
通讯作者：
Li JX
中科院分区：
文献类型：
--
作者：
Siemian JN;Li J;Zhang Y;Li JX
最近的证据表明，咪唑啉I2受体配体适合与阿片类药物联合治疗。I2受体配体与非阿片类药物联合应用的定量分析对于替代性疼痛治疗的合理性是必要的。本研究系统地研究了选择性I2受体配体（2-BFI和苯唑啉）单独使用和与对乙酰氨基酚联合使用的抗痛觉过敏和反应率抑制作用。采用Von Frey和Hargreaves试验检测药物对完全弗氏佐剂（CFA）诱导的大鼠炎性痛的抗痛觉过敏作用。使用食物强化的时间表控制反应来评估研究药物的心率抑制作用。使用剂量相加和等效线分析评估所有试验的药物相互作用。2-BFI（3.2-17.8 mg/kg，腹腔注射），苯唑啉（17.8-100 mg/kg，i. p.），和对乙酰氨基酚（56-178 mg/kg，i. p.）所有的剂量依赖性地产生显著的抗伤害感受作用。当作为组合进行研究时，2-BFI和对乙酰氨基酚产生了加性与加性之间的相互作用，而苯唑啉和对乙酰氨基酚产生了加性与超加性之间的相互作用。相同的药物组合以超累加方式抑制应答率。抗痛觉过敏和反应率抑制作用的定量分析表明，I2受体配体不太适合与对乙酰氨基酚联合治疗。
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 justification of alternative pain therapies. This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Von Frey and Hargreaves tests were used to examine the anti-hyperalgesic 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. 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. Quantitative analysis of the anti-hyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen.