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Pharmacological Insights into the Use of Apomorphine in Parkinson’s Disease: Clinical Relevance

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Abstract

The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson’s disease (PD). The chemistry, structure–activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic. Its pharmacokinetics and pharmacodynamics are complex and subject to interindividual variability, particularly for subcutaneous absorption and metabolism. Subcutaneous apomorphine, either as injections or infusion, is particularly useful for the treatment of PD motor symptoms and growing evidence supports its clinical value for nonmotor disorders. Owing to interindividual variability and sensitivity, apomorphine treatment must be tailored to each patient. While the subcutaneous route has been the gold standard for decades, the search for alternative routes is ongoing, with promising results from studies of pulmonary, sublingual and transdermal routes. In addition, the potential of apomorphine as a disease-modifying therapy deserves to be investigated, as well as its ability to induce brain plasticity through chronic infusion. Moreover, the ongoing progress in the development of analytical methods should be accompanied by new pharmacokinetic and pharmacodynamic studies of apomorphine metabolism and sites of action in humans, as its biochemistry has yet to be fully described.

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Notes

  1. Dopamine itself is a dihydroxyphenylethylamine.

  2. For a comprehensive review of existing methods of apomorphine administration, please see [35].

  3. Today known as chronic nephritis.

  4. E.g. domperidone, sorafenib, triptorelin, rilpivirine, quinine, quetiapine, pasireotide, osimertinib, oldaterol, nafarelin, mifepristone, leuprolide, lenvatinib, indacaterol, histrelin, haloperidol, goserelin, fluoxetine, ezogabine, critozinib, citalopram, bedaquiline, vemurafenib, vilanterol, toremifene, saquinavir, and panobinostat.

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Acknowledgments

Mrs. Elizabeth Portier-Wiles edited the manuscript for non-intellectual content.

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Authors and Affiliations

  1. “Behavior and Basal Ganglia” Research Unit (EA 4712), University of Rennes 1, Rennes, France

    Manon Auffret, Sophie Drapier & Marc Vérin

  2. Movement Disorders Unit, Neurology Department, Pontchaillou University Hospital, Rennes, France

    Sophie Drapier & Marc Vérin

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Dr Manon Auffret: none. Dr Sophie Drapier served on scientific advisory boards for Orkyn and Aguettant, received speech honorarium from Orkyn, Aguettant, Medtronic, Teva and received PHRC grants from the French Ministry of Health.Pr Marc Vérin served on scientific advisory boards for Orkyn and Aguettant and received speech honorarium from Orkyn, Aguettant, Medtronic and Teva.

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Auffret, M., Drapier, S. & Vérin, M. Pharmacological Insights into the Use of Apomorphine in Parkinson’s Disease: Clinical Relevance. Clin Drug Investig 38, 287–312 (2018). https://doi.org/10.1007/s40261-018-0619-3

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