Colosimo C, Merello M, Albanese A
Istituto di Neurologia, Università Cattolica del Sacro Cuore, Roma, Italy.
Clin Neuropharmacol. 1994 Jun;17(3):243-59. doi: 10.1097/00002826-199406000-00004.
Apomorphine, the first dopamine agonist to be synthesized, has received a renewed interest in the last few years. This compound acts powerfully on D1 and D2 dopamine receptors and has the most complete pharmacological profile of all clinically available dopamine agonists. When given subcutaneously, apomorphine consistently reverses levodopa-resistant "off" periods in parkinsonian subjects: thus, it is used in cases with severe motor fluctuations, either by continuous infusion with a portable pump or by multiple injections. Studies based on this approach have been highly encouraging, as they have shown a significant reduction in off time and a good drug tolerability. The main side effect has been the occurrence of nodular skin lesions, especially when continuous infusions were used. At variance with other dopamine agonists, a low incidence of psychiatric morbidity has been reported with apomorphine. The few available comparative reports have shown that this compound is more potent and better tolerated than lisuride. Parenteral apomorphine has been used in Parkinson's disease (PD) to replace levodopa after surgery or to treat the malignant syndrome brought about by sudden levodopa withdrawal. Acute challenge with apomorphine has been used to test dopaminergic responsiveness in parkinsonian syndromes and in dystonia. The clinical response to apomorphine may predict the effect of a chronic therapy with levodopa in approximately 90% of PD cases. Further studies are still necessary to evaluate the exact relationship between the acute response to apomorphine and a chronic therapy. In addition, apomorphine has been used to conduct clinical pharmacological studies in PD, for it is particularly well suited for research on the pharmacodynamics of central dopamine receptors. In summary, apomorphine appears to be an efficacious and safe drug for the treatment of advanced PD. It must still be considered under clinical evaluation as a test drug for acute challenge in PD and dystonia. Finally, in our opinion, the available data suggest apomorphine (in conjunction with domperidone) as a first-choice treatment for the neuroleptic malignant syndrome and the temporary replacement of levodopa (e.g., after gastrointestinal surgery).
阿扑吗啡是首个合成的多巴胺激动剂，在过去几年中重新受到关注。该化合物对D1和D2多巴胺受体有强大作用，且在所有临床可用的多巴胺激动剂中具有最完整的药理学特征。皮下注射时，阿扑吗啡能持续逆转帕金森病患者对左旋多巴耐药的“关”期：因此，它用于治疗严重运动波动的病例，可通过便携式泵持续输注或多次注射给药。基于这种方法的研究非常令人鼓舞，因为它们显示“关”期时间显著缩短且药物耐受性良好。主要副作用是出现结节性皮肤病变，尤其是在使用持续输注时。与其他多巴胺激动剂不同，据报道阿扑吗啡引起精神疾病的发生率较低。少数可用的比较报告表明，该化合物比利苏来得更有效且耐受性更好。胃肠外阿扑吗啡已用于帕金森病（PD），在手术后替代左旋多巴或治疗因突然停用左旋多巴引起的恶性综合征。阿扑吗啡急性激发试验已用于测试帕金森综合征和肌张力障碍中的多巴胺能反应性。在约90%的PD病例中，对阿扑吗啡的临床反应可预测左旋多巴长期治疗的效果。仍需进一步研究以评估阿扑吗啡急性反应与长期治疗的确切关系。此外，阿扑吗啡已用于PD的临床药理学研究，因为它特别适合用于中枢多巴胺受体药效学的研究。总之，阿扑吗啡似乎是治疗晚期PD的一种有效且安全的药物。在PD和肌张力障碍的急性激发试验中，它仍必须作为试验药物接受临床评估。最后，我们认为现有数据表明阿扑吗啡（与多潘立酮联用）是治疗抗精神病药恶性综合征和临时替代左旋多巴（如在胃肠道手术后）的首选治疗方法。
