Rasagilin in der klinischen Anwendung

Zusammenfassung

Rasagilin ist ein MAO-B-Hemmer der zweiten Generation, der in Zellkultur und im Tiermodell neuroprotektive Eigenschaften aufweist. Er führt nicht zum Abbau zu Amphetamin und Methamphetamin, wie dies bei Selegilin der Fall ist. Es handelt sich um einen irreversiblen Hemmer, der beim Parkinson-Patienten zur Anwendung kommt. In Denovo-Patienten konnte in der TEMPO-Studie ein “disease modifying process” gezeigt werden, der für eine neuroprotektive Wirkung der Substanz auch beim Menschen spricht. Die Wirksamkeit erscheint etwa sechsmal so hoch wie dies für Selegilin bekannt ist. In fortgeschrittenen Stadien führt Rasagilin entsprechend den Studien LARGO und PRESTO ebenfalls zu einer Verbesserung der Motorik, inklusive des “freezing of gait” und der morgendlichen Akinese. Die neue Substanz hat keine nennenswerten Nebenwirkungen und scheint eine Anit-Fatigue-Wirkung zu besitzen. Im täglichen Umgang sprechen die ersten eigenen Erfahrungen für eine wertvolle neue Option in der Behandlung der Parkinson-Krankheit.

Summary

Rasagiline can be called a MAO-B-inhibitor of the second generation. It has shown both in cell culture and animal models neuroprotective properties. Rasagilin is not transverted to amphetamine or methamphetamine as is the case for selegiline. It causes irreversible inhibition of the MAO. In de novo patients rasagiline proved to bea disease modifying agent (TEMPO study) and there is good reason to call this neuroprotection. The efficacy is about six times higher than known for selegiline. In advanced Parkinson’s disease (PD) rasagiline also lead to improvement of motor symptoms and as well of freezing of gait and early morning akinesia. The new substance has anti-fatigue properties. In daily practice rasagiline seems to become a valuable new option for the treatment of PD.

Schlüsselwörter

Parkinson Krankheit - MAO-B Hemmer - Rasagilin - Neuroprotektion

Keywords

Parkinson’s disease - MAO-B inhibition - rasagiline - neuroprotection

• Literatur

• 1 Del Tredici K, Rub U, De Vos RA, Bohl JR, Braak H. Where does parkinson disease pathology begin in the brain?. J Uropathol Exp Neurol 2002; 61: 413-26.
• 2 Diener HC. et al. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart, New York: Thieme; 2003
• 3 Larsen JP, Boas J, Erdal JE. Norwegian-Danish Study Group. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. Eur J Neurol 1999; 06: 539-47.
• 4 Müller A, Müngersdorf M, Reichmann H. et al. Olfactory function in Parkinsonian syndromes. J Clin Neurosci 2002; 09: 521-4.
• 5 Müller A, Reichmann H, Livermore A, Hummel T. Olfactory function in idiopathic Parkinson’s disease (IPD): results from cross-sectional studies in IPD patients and long-term follow-up of de-novo IPD patients. J Neural Transm 2002; 109: 805-11.
• 6 Müller A, Abolmaali N, Hummel T, Reichmann H. Riechstörungen – ein frühes Kardinalsymptom des idiopathischen Parkinson-Syndroms. Akt Neurol 2003; 30: 239-43.
• 7 Olanow CW. et al. The effect of deprenyl and levodopa on the progression of Parkinson’s disease. Ann Neurol 1997; 38: 771-7.
• 8 Parkinson Study Group A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Arch Neurol. 2002; 59: 1937-43.
• 9 Parkinson Study Group. A controlled, randomised, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 2004; 61: 561-6.
• 10 Parkinson Study Group. A randomised placebocontrolled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations. Arch Neurol 2005; 62: 241-8.
• 11 Rascol O. et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily, study): a randomized, double-blind, parallel-group trial. Lancet 2005; 365: 947-54.
• 12 Riederer P, Lachenmayer L. Selegiline’s neuroprotective capacity revisited. J Neural Transm 2003; 110: 1273-8.
• 13 Sommer U. et al. Parkinson’s diseae as possible cause of “idiopathic” olfactory dysfunction. Mov Disord 2002; 17 (Suppl. 05) S151.
• 14 Sommer U, Hummel T, Cormann K. et al. Detection of presymptomatic Parkinson’s disease: Combining smell tests, transcranial sonography, and SPECT. Mov Disord 2004; 19: 1196-202.
• 15 Marek K. et al. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA 2002; 287: 1653-61.
• 16 Uitti RJ. et al. Amantadine treatment is an independent predictor of improved survival in Parkinson’s disease. Neurology 1996; 46: 1551-6.
• 17 Waters CH. et al. Zydis selegiline reduces off time in Parkinson’s disease patients with motor fluctuations: a 3-month, randomized, placebo-controlled study. Mov Disord 2004; 19: 426-32.
• 18 Whone AL, Watts RL, Stoessl AJ. The REAL-PET Study Group. Slower progression of Parkinson’s disease with ropinirole versus levodopa: The REAL-PET study. Ann Neurol 2003; 54: 93-101.