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Synergistic antinociception of propofol-alfentanil combination in mice

机译:丙泊酚-芬太尼组合的协同镇痛作用

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Drug combination is frequently used in pain treatment, which can produce similar analgesia with reduced dosage and side effects. In the present study, we examined the effects of co-administration of propofol, a general anesthetic, and alfentanil, an opioid analgesic drug, and the types of interactions between them in heat induced acute phasic and acetic-acid induced acute tonic pain models using the up-and-down method. In both pain models, alfentanil was administered in fixed-dose fractions of the 50% effective dose (ED_(50)), and the types of interactions were determined by isobolographic analysis. In hot plate test, alfentanil (35.6-50.0 ug/kg, i.v.), propofol (6.5-15.5 mg/kg, i.v.), and their combinations (80%, 50%, 30% and 10% of a single drug ED_(50)) produce a significant, dose-dependent antinociception. In the tail-flick test, alfentanil (35.6-50.0 ug/kg, i.v.), propofol (5.0-14.3 mg/kg, i.v.), and their combination significantly and dose dependently extend the tail-flick latency. In the acetic-acid induced writhing test, alfentanil (12.5-23.2 ug/kg, i.p.), propofol (15.0-28.5 mg/kg, i.p.), and their combination significantly and dose dependently reduce the frequency of writhing. In all the above pain models, isobolographic analysis revealed a significant synergistic interaction between alfentanil and propofol, with about 4-fold reduction of doses of both drugs, in comparison with each single drug's ED_(50). These data suggest that the combination of alfentanil and propofol synergistically suppresses acute phasic and tonic pain in mice, indicating a potential application in pain treatment.
机译:药物组合常用于疼痛治疗,可产生类似的镇痛效果,但剂量和副作用却减少。在本研究中,我们研究了丙泊酚(全麻)和阿芬太尼(阿片类镇痛药)的共同给药效果,以及它们在热诱导的急性阶段性和乙酸引起的急性强直性疼痛模型中的相互作用类型。上下方法。在两种疼痛模型中,均以50%有效剂量(ED_(50))的固定剂量部分给药阿芬太尼,并通过等效线描记法分析确定相互作用的类型。在热板测试中,阿芬太尼(35.6-50.0 ug / kg,iv),丙泊酚(6.5-15.5 mg / kg,iv)及其组合(一种药物的ED_(80%,50%,30%和10%) 50))产生明显的剂量依赖性抗伤害感受。在甩尾试验中,阿芬太尼(35.6-50.0 ug / kg,静脉内),丙泊酚(5.0-14.3 mg / kg,静脉内)及其组合显着且剂量依赖性地延长了甩尾潜伏期。在乙酸诱导的扭体试验中,阿芬太尼(12.5-23.2 ug / kg,i.p.),丙泊酚(15.0-28.5 mg / kg,i.p.)及其组合可显着降低剂量并减少扭体次数。在上述所有疼痛模型中,等效线描记法分析显示,与每种单一药物的ED_(50)相比,阿芬太尼和丙泊酚之间存在显着的协同作用,两种药物的剂量均降低了约4倍。这些数据表明,阿芬太尼和丙泊酚的组合可协同抑制小鼠的急性阶段性和强直性疼痛,表明在疼痛治疗中有潜在的应用。

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