Unterschiedliche Rezeptorprofile der Dopaminagonisten und klinische Auswirkungen

Zusammenfassung

Dopaminagonisten haben einen festen Platz in der Behandlung von Patienten mit Morbus Parkinson. Der frühe Einsatz dieser Medikamente kann das Auftreten von Dyskinesien deutlich verzögern und die Schwere dieser Störungen reduzieren. Ob diese Medikamente eine neuroprotektive Wirkung haben, kann auf Basis der vorliegenden Daten nicht ausreichend beurteilt werden. Bisher hing die Wahl des Dopaminagonisten vor allem von der Erfahrung des behandelnden Arztes ab, da die klinischen Studien keine sicheren Unterschiede bezüglich Wirksamkeit und Nebenwirkungen aufzeigen konnten. Basierend auf der chemischen Struktur werden die Dopaminagonisten in Ergotalkaloide und nicht-Ergotalkaloide unterschieden. Während die Ergotalkaloide eine alle eine relativ ähnliche molekulare Struktur aufweisen, die von anderen Mutterkornalkaloiden abgeleitet ist, sind die nicht-Ergotalkaloide eine heterogene Gruppe. Neuere Befunde deuten darauf hin, dass die Ergotalkaloide nicht nur an den Dopaminrezeptoren agonistisch wirken, sondern auch auf adrenerge und serotonerge Rezeptoren wirken. Ob durch diese „unspezifische” Wirkung ein höheres Risiko in der Langzeittherapie besteht, muss in der Zukunft geklärt werden.

Abstract

Dopamine agonists are increasingly being used in the treatment of patients with Parkinson's disease (PD) because they provide symptom relief and a low risk to induce dyskinesia. Whether these drugs also exhibit neuroprotective properties remains unclear based on the present data. The choice among the many dopamine agonists was, thus far, mainly dependent on the physician's experience with individual compounds since clinical trials did not reveal relevant differences in respect to clinical efficacy or safety. Dopamine agonists are divided into two groups: ergot-derivatives and non ergot-derivatives. While ergot-derivatives share a similar molecular structure derived from other ergots, non-ergot-derivatives are a group of heterogenous compounds. Ergot-alkaloids not only stimulate dopamine receptors but also adrenergic and serotonergic receptors. Whether stimulation of such „non-specific” receptors causes long-term safety issues needs to be investigated.

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