Introduction to Apomorphine and its Role in the Treatment of Parkinson’s Disease
Professor of Neurology, National Hospital for Neurology and Neurosurgery, London.
Apomorphine is a highly-potent dopamine agonist (DA) that, unlike other clinically available compounds in this class, selectively acts on both D1 and D2 dopamine receptors and has been shown in a number of published clinical trials to achieve antiparkinsonian efficacy comparable to that of orally administered levodopa.1 As far back as the 1950s, apomorphine was used to treat PD, long before its dopaminergic properties were fully understood and levodopa was developed.2 Subsequently, in the late 1960s, Cotzias and colleagues, aware of some of the shortcomings of levodopa in PD treatment, began to investigate other dopaminergic compounds and conducted clinical investigations into apomorphine in PD patients. They found that tremor responded well to apomorphine therapy, that it reduced dyskinesias in levodopa-treated patients and that it had possible anti-psychotic properties.3 The product was not developed further at that time as a therapy for PD, possibly due to both the emergence of oral dopaminergic drugs and the reluctance of neurologists to use an injectable formulation, but also due to its emetic properties. Subsequently, as a result of new pump technology in the field of diabetes and the availability of the anti-emetic domperidone, a clinical trial of apomorphine infusion for the management of Parkinsonian ON-OFF oscillations was undertaken by Stibe and colleagues.4 Published in 1988, this pivotal trial confirmed that apomorphine was the only clinically available DA that was equipotent to levodopa and it was subsequently licensed for the treatment of PD in the UK. Since that time, a range of randomised, controlled clinical trials (using apomorphine injection) and open, uncontrolled studies (using apomorphine infusion) have confirmed it as a highly effective therapy to help manage refractory motor fluctuations, with thousands of PD patients throughout the world benefitting from its use. Apomorphine infusion has also been shown to improve drug-induced dyskinesias, allowing a reduction in the oral levodopa dose.5 Nowadays, apomorphine is recognised by clinicians as an established therapy, backed by many patient-years of experience, which still has considerable value in helping to manage the complex problems they face in treating PD patients in their daily clinical practice.
This satellite symposium, held during the 18th International Congress of Parkinson’s Disease and Movement Disorders, reviewed the extensive clinical experience with subcutaneous apomorphine in PD patients that has accumulated over the past 25 years and explored why it continues to play such a valuable role in treatment of this disease.
While the management of PD focuses primarily on addressing motor symptoms, there is also a broad range of non-motor symptoms (NMS) that compromise health-related quality of life (QoL) in PD patients.6–8 In his presentation, Professor K Ray Chaudhuri discussed comparative data on both motor and non-motor effects of conventional non-oral/ transdermal therapies in advanced PD and the reported beneficial effects of subcutaneous apomorphine in this setting, particularly in terms of its side-effect profile in comparison to other agents.
Morning akinesia is a common but under-recognised symptom in PD patients, which occurs in almost 60 % of subjects9 and results from a delay in time to ON (TTO) of the first daily dose of levodopa. Professor Stuart Isaacson reviewed the interim results from the ongoing AM-IMPAKT study that demonstrate that subcutaneous apomorphine injection results in a rapid and reliable TTO in these patients, with significant improvements in QoL.