Clinic for Anaesthesia and Critical Care Medicine, OE 8050, Hannover, Germany.
Pharmacology. 2011;87(1-2):115-20. doi: 10.1159/000323557. Epub 2011 Feb 1.
Paracetamol (acetaminophen) is a widely used antipyretic and analgesic drug for mild or moderate pain states. As the primary site of action of paracetamol is still the subject of ongoing discussion, the focus of this study is the investigation of a potential mechanism which might contribute to its beneficial effects in the therapy of pain. Loss of inhibitory synaptic transmission within the dorsal horn of the spinal cord plays a key role in the development of pain following inflammation or nerve injury. Inhibitory postsynaptic transmission in the adult spinal cord involves mainly glycine. In this study we investigated the interaction of paracetamol with strychnine-sensitive α(1)-glycine receptors (α(1)-GlyR). α(1)-GlyR subunits transiently expressed in HEK-293 cells were studied using the whole-cell patch-clamp technique and a piezo-controlled liquid filament fast application system. Paracetamol fails to show a positive allosteric modulatory effect in low nano- to micromolar concentrations and lacks direct activation in micromolar concentrations at the α(1)-GlyR. Consequently, the analgesic actions of paracetamol leading to pain relief appear to be mediated via other mechanisms, but not via activation of spinal glycinergic pathways.
对乙酰氨基酚（扑热息痛）是一种广泛用于治疗轻度或中度疼痛的解热镇痛药。由于对乙酰氨基酚的主要作用部位仍在讨论中，本研究的重点是研究一种可能有助于其在疼痛治疗中发挥有益作用的潜在机制。脊髓背角抑制性突触传递的丧失在炎症或神经损伤后疼痛的发展中起着关键作用。成人脊髓中的抑制性突触传递主要涉及甘氨酸。在这项研究中，我们研究了对乙酰氨基酚与士的宁敏感的 α(1)-甘氨酸受体（α(1)-GlyR）的相互作用。使用全细胞膜片钳技术和压电控制的液体细丝快速施加系统，研究了在 HEK-293 细胞中瞬时表达的 α(1)-GlyR 亚基。在低纳摩尔至微摩尔浓度下，对乙酰氨基酚未显示出正变构调节作用，在微摩尔浓度下也缺乏直接激活作用在 α(1)-GlyR 上。因此，对乙酰氨基酚的镇痛作用导致疼痛缓解似乎是通过其他机制介导的，而不是通过激活脊髓甘氨酸能途径。
