Bhagyashree A, Manikkoth Shyamjith, Sequeira Melinda, Nayak Roopa, Rao S N
Department of Pharmacology, Yenepoya Medical College, Mangalore, Karnataka, India.
Indian J Pharmacol. 2017 Jan-Feb;49(1):21-25. doi: 10.4103/0253-7613.201029.
Even after 100 years of discovery, the exact mechanisms for the analgesic action of paracetamol are under scanner. It was recently proposed that paracetamol may act through different mechanisms, especially altering the serotoninergic system. The main objective of this preclinical study was to verify the role of drugs modulating dopaminergic system (l-dopa, bromocriptine, olanzapine) on the analgesic effect of paracetamol.
Thirty adult male albino mice were divided into five groups: distilled water (0.5 ml/25 g), paracetamol (200 mg/kg), levodopa (10 mg/kg) + paracetamol, bromocriptine (5 mg/kg) + paracetamol (200 mg/kg), and olanzapine (2 mg/kg) + paracetamol (200 mg/kg). All drugs were administered orally for 14 days. Eddy's hot plate and tail immersion tests were used to determine analgesic activity. Tests were conducted 1 h after the drug administration on the 14 day. After that, animals were sacrificed and brains were dissected out, to measure the levels of dopamine. Statistical comparisons among the groups were performed by one-way analysis of variance followed by Tukey-Kramer test.
Coadministration of l-dopa and bromocriptine with paracetamol increased the antinociceptive activity of paracetamol significantly, whereas coadministration of olanzapine with paracetamol decreased the analgesic activity of paracetamol in the Eddy's hot plate and tail immersion tests considerably. There was a significant increase ( < 0.001) in the levels of dopamine in the brains of mice, which received levodopa, bromocriptine, and paracetamol. However, it was opposite in the brains of animals which received olanzapine.
The results suggest that analgesic action of paracetamol is influenced by dopaminergic system.
即便在发现对乙酰氨基酚100年后，其镇痛作用的确切机制仍在研究之中。最近有人提出，对乙酰氨基酚可能通过不同机制发挥作用，尤其是改变5-羟色胺能系统。这项临床前研究的主要目的是验证调节多巴胺能系统的药物（左旋多巴、溴隐亭、奥氮平）对对乙酰氨基酚镇痛效果的作用。
30只成年雄性白化病小鼠被分为五组：蒸馏水（0.5毫升/25克）、对乙酰氨基酚（200毫克/千克）、左旋多巴（10毫克/千克）+对乙酰氨基酚、溴隐亭（5毫克/千克）+对乙酰氨基酚（200毫克/千克）、奥氮平（2毫克/千克）+对乙酰氨基酚（200毫克/千克）。所有药物均口服给药，持续14天。采用Eddy热板法和尾浸法测定镇痛活性。在第14天给药1小时后进行测试。之后，处死动物并取出大脑，以测量多巴胺水平。组间统计比较采用单因素方差分析，随后进行Tukey-Kramer检验。
在Eddy热板法和尾浸法测试中，左旋多巴和溴隐亭与对乙酰氨基酚联合使用显著增强了对乙酰氨基酚的镇痛活性，而奥氮平与对乙酰氨基酚联合使用则显著降低了对乙酰氨基酚的镇痛活性。接受左旋多巴、溴隐亭和对乙酰氨基酚的小鼠大脑中多巴胺水平显著升高（<0.001）。然而，接受奥氮平的动物大脑中情况则相反。
结果表明，对乙酰氨基酚的镇痛作用受多巴胺能系统影响。
