Clinical usefulness of apomorphine in movement disorders

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).