Department of Medical Biophysics, Comenius University in Bratislava, Martin, Slovakia.
Adv Exp Med Biol. 2013;756:65-71. doi: 10.1007/978-94-007-4549-0_9.
Opioid receptors which are involved in cough generation are abundantly expressed in the brainstem. Codeine is a potent μ-opioid receptor agonist. In the present study we examined the effects of naloxone, a μ-opioid receptor antagonist, on mechanically-induced tracheobronchial cough and on the cough suppressing effect of codeine in six pentobarbitone anesthetized spontaneously breathing rabbits. A single dose of naloxone (0.4 mg/kg) followed by a single dose of codeine (7 mg/kg) were administered intravenously. The number and amplitude of cough and sneeze reflexes were examined sequentially; before and after naloxone, and then after codeine. We found that neither did naloxone alone nor codeine given after prior naloxone pretreatment appreciably affect coughing or sneezing. Likewise, there were no significant differences in the diaphragm and abdominal muscles electromyographic moving averages, or the inspiratory and expiratory esophageal pressure amplitudes. However, we detected a tendency for the rise in expiratory motor drive during coughing and sneezing after injection of naloxone. The respiratory rate was significantly higher after naloxone in comparison with control (P < 0.001). No significant differences in arterial blood pressure were observed. We conclude that the failure of codeine to suppress the cough reflex on the background of naloxone pretreatment confirms the involvement of μ-opioid mechanism in the central antitussive effect of codeine.
阿片受体参与咳嗽的产生，在脑干中大量表达。可待因是一种强效的μ-阿片受体激动剂。在本研究中，我们研究了纳洛酮（一种μ-阿片受体拮抗剂）对机械性诱发的气管支气管咳嗽的影响，以及纳洛酮预处理后可待因对咳嗽的抑制作用，共涉及六只戊巴比妥麻醉的自主呼吸兔。静脉注射单剂量纳洛酮（0.4mg/kg）和单剂量可待因（7mg/kg）。依次检查咳嗽和喷嚏反射的次数和幅度；在纳洛酮之前、之后，以及可待因之后。我们发现，纳洛酮单独使用或在纳洛酮预处理后给予可待因均不能显著影响咳嗽或喷嚏。同样，膈肌和腹肌肌电图移动平均值，或吸气和呼气食管压力幅度也没有显著差异。然而，我们在注射纳洛酮后检测到咳嗽和喷嚏时呼气运动驱动力升高的趋势。与对照相比，纳洛酮后呼吸频率显著升高（P < 0.001）。动脉血压无明显差异。我们的结论是，纳洛酮预处理后可待因不能抑制咳嗽反射，证实了μ-阿片机制参与了可待因的中枢镇咳作用。
