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.
Literatur
1
Schwab R S, Amador L V, Lettvin J Y.
Apomorphine in Parkinson's disease.
Trans Am Neurol Assoc.
1951;
76
251
2
Parkinson-Study-Group .
A randomized controlled trial comparing pramipexole with levodopa in early Parkinson's disease: design and methods of the CALM-PD Study. Parkinson Study Group.
Clin Neuropharmacol.
2000;
23
34-44
3
Malcolm R, Kajdasz D K, Herron J. et al .
A double-blind, placebo-controlled outpatient trial of pergolide for cocaine dependence.
Drug Alcohol Depend.
2000;
60
161-168
4
Frucht S, Rogers J D, Greene P E. et al .
Falling asleep at the wheel: motor vehicle mishaps in persons taking pramipexole and ropinirole.
Neurology.
1999;
52
1908-1910
5
Camp G van, Flamez A, Cosyns B. et al .
Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease.
Lancet.
2004;
363
1179-1183
6
Parkinson's-Disease-Research-Group-of-the-United-Kingdom .
Comparison of therapeutic effects of levodopa, levodopa and selegiline, and bromocriptine in patients with early, mild Parkinson's disease. Is rapid titration preferable to slow?.
Neurology.
1993;
52
1227-1229
7
Lees A J, Katzenschlager R, Head J. et al .
Ten year follow-up of three different initial treatments in de-novo PD: a randomized trial.
Neurology.
2001;
57
1687-1694
8
Montastruc J L, Rascol O, Rascol A.
A randomised controlled study of bromocriptine versus levodopa in previously untreated parkinsonian patients: a 3 year follow-up.
J Neurol Neurosurg Psychiatry.
1989;
52
773-775
10
Montastruc J L, Rascol O, Senari J M, Rascol A.
A randomized trial comparing bromocriptine to which levodopa was later added, with levodopa alone in previously untreated patients with Parkinson's disease: a five year follow-up.
J Neurol Neurosurg Psychiatry.
1994;
57
1034-1038
11
Laihinen A, Rinne U K, Suchy I.
Comparison of lisuride and bromocriptine in the treatment of advanced Parkinson's disease.
Acta Neurol Scand.
1992;
86
593-595
12
Oertel W H, Schwarz J, Leenders K L. et al .
Results of a 3-year randomized, double-blind, PET-controlled study of pergolide vs. L-dopa as monotherapy in early Parkinson's Disease (PELMOPET-trial).
J Neurol Sci.
2001;
187
S444
13
Barone P, Bravi D, Bermejo-Pareja F. et al .
Pergolide monotherapy in the treatment of early PD: a randomized, controlled study. Pergolide Monotherapy Study Group.
Neurology.
1999;
53
573-579
14
Kulisevsky J, Lopez-Villegas D, Garcia-Sanchez C. et al .
A six-month study of pergolide and levodopa in de novo Parkinson's disease patients.
Clin Neuropharmacol.
1998;
21
358-362
15 Clarke C E, Speller J M. Pergolide versus bromocriptine for levodopa-induced motor complications in Parkinson's disease. Cochrane Database Syst Rev 2000; CD000236
17
Pezzoli G, Martignoni E, Pacchetti C. et al .
A crossover, controlled study comparing pergolide with bromocriptine as an adjunct to levodopa for the treatment of Parkinson's disease.
Neurology.
1995;
45
S22-27
18
Olanow C W, Alberts M J.
Double-blind controlled study of pergolide mesylate as an adjunct to Sinemet in the treatment of Parkinson's disease.
Adv Neurol.
1987;
45
555-560
19
Rinne U K, Bracco F, Chouza C. et al .
Cabergoline in the treatment of early Parkinson's disease: results of the first year of treatment in a double-blind comparison of cabergoline and levodopa. The PKDS009 Collaborative Study Group.
Neurology.
1997;
48
363-368
21
Hutton J T, Koller W C, Ahlskog J E. et al .
Multicenter, placebo-controlled trial of cabergoline taken once daily in the treatment of Parkinson's disease.
Neurology.
1996;
46
1062-1065
23
Steiger M J, El-Debas T, Anderson T. et al .
Double-blind study of the activity and tolerability of cabergoline versus placebo in parkinsonians with motor fluctuations.
J Neurol.
1996;
243
68-72
24
Bergamasco B, Frattola L, Muratorio A. et al .
Alpha-dihydroergocritpine in the treatment of de novo parkinsonian patients: results of a multicenter, randomized, double-blind, placebo-controlled study.
Acta Neurol Scand.
2000;
101
372-380
25
Battistin L, Bardin P G, Ferro-Milone F. et al .
Alpha-dihydroergocritpine in Parkinson's disease: a multicenter, randomized, double-blind, parallel-group study.
Acta Neurol Scand.
1999;
99
36-42
26
Whone A L, Watts R L, Stoessl A J. et al .
Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study.
Ann Neurol.
2003;
54
93-101
27
Rascol O, Brooks D J, Korczyn A D. et al .
A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa. 056 Study Group.
N Engl J Med.
2000;
342
1484-1491
28
Im J H, Ha J H, Cho I S, Lee M C.
Ropinirole as an adjunct to levodopa in the treatment of Parkinson's disease: a 16-week bromocriptine controlled study.
J Neurol.
2003;
250
90-96
29
Brunt E R, Brooks D J, Korczyn A D. et al .
A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa.
J Neural Transm.
2002;
109
489-502
30 Clarke C E, Deane K H. Ropinirole versus bromocriptine for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev 2001; CD001517
31
Rascol O, Lees A J, Senari J M. et al .
A placebo-controlled study of ropinirole, a new D2 agonist, in the treatment of motor fluctuations of L-DOPA-treated parkinsonian patients.
Adv Neurol.
1996;
69
531-534
32
Pinter M M, Pogarell O, Oertel W H.
Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: a double blind, placebo controlled, randomised, multicentre study.
J Neurol Neurosurg Psychiatry.
1999;
66
436-441
33 Clarke C E, Speller J M, Clarke J A. Pramipexole versus bromocriptine for levodopa-induced complications in Parkinson's disease. Cochrane Database Syst Rev 2000; CD002259
34
Dewey Jr R B, Hutton J T, LeWitt P A, Factor S A.
A randomized, double-blind, placebo-controlled trial of subcutaneously injected apomorphine for parkinsonian off-state events.
Arch Neurol.
2001;
58
1385-1392
35
Colzi A, Turner K, Lees A J.
Continuous subcutaneous waking day apomorphine in the long-term treatment of levodopa induced interdose dyskinesias in Parkinson's disease.
J Neurol Neurosurg Psychiatry.
1998;
64
573-576
37
Millan M J, Maiofiss L, Cussac D. et al .
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes.
J Pharmacol Exp Ther.
2002;
303
791-804
38
Gerlach M, Double K, Arzberger T. et al .
Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum.
J Neural Transm.
2003;
110
1119-1127
39
Newman-Tancredi A, Cussac D, Audinot V. et al .
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D(2)-like receptor and alpha(1)/alpha(2)-adrenoceptor.
J Pharmacol Exp Ther.
2002;
303
805-814
40
Newman-Tancredi A, Cussac D, Quentric Y. et al .
Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.
J Pharmacol Exp Ther.
2002;
303
815-822
41
Fitzgerald L W, Burn T C, Brown B S. et al .
Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine.
Mol Pharmacol.
2000;
57
75-81
42
Xu J, Jian B, Chu R. et al .
Serotonin mechanisms in heart valve disease II: the 5-HT2 receptor and its signaling pathway in aortic valve interstitial cells.
Am J Pathol.
2002;
161
2209-2218
