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New pharmacotherapy for Parkinson's disease.
Ann Pharmacother. 1997 Oct; 31(10):1205-17.AP

Abstract

OBJECTIVE

To summarize the development, pharmacology, pharmacokinetics, efficacy, and safety of five investigational antiparkinsonian drugs that are in or have recently completed Phase III trials: three dopamine agonists, pramipexole, ropinirole, and cabergoline; and two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone. The pathophysiology and the role of dopamine in Parkinson's disease are also reviewed.

DATA SOURCES

A MEDLINE search of relevant English-language literature, clinical studies, abstracts, and review articles pertaining to Parkinson's disease was conducted. Manual searches of 1996/1997 meeting abstracts published by the American Academy of Neurology and the Movement Disorders Society were also performed. Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic data.

STUDY SELECTION AND DATA EXTRACTION

Clinical trial investigations selected for inclusion were limited to human subjects. Interim analyses after 6 months for long-term clinical studies in progress were included. Pharmacokinetic data from animals were cited if human data were unavailable. Statistical analyses for all studies were evaluated.

DATA SYNTHESIS

By selectivity targeting D2 receptors, the newer dopamine agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the introduction of levodopa and thus the occurrence of levodopa-induced dyskinesias. In addition, they are efficacious as adjunctive therapies in patients with advanced Parkinson's disease. Unlike the currently available dopamine agonists, pramipexole and ropinirole are non-ergot derivatives and do not cause skin inflammation, paresthesias, pulmonary infiltrates, or pleural effusion. The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson's disease.

CONCLUSIONS

Interim 6-month analyses of pramipexole, ropinirole, and cabergoline for symptomatic treatment of early Parkinson's disease have shown these drugs to be efficacious and relatively well-tolerated when used as monotherapy. Their role in delaying the development of motor fluctuations and delaying the addition of levodopa is the subject of long-term clinical studies. In advanced stages of Parkinson's disease, these medications were also efficacious; however, the main adverse effects included dyskinesias, somnolence, and hallucinations. The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone has also demonstrated efficacy in patients with motor fluctuations. Both drugs are relatively well-tolerated, with the exception of dyskinesias that require reduction of the levodopa dosage and occasional diarrhea.

Authors+Show Affiliations

Department of Clinical Pharmacy, University of California, San Francisco 94143, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

9337447

Citation

Gottwald, M D., et al. "New Pharmacotherapy for Parkinson's Disease." The Annals of Pharmacotherapy, vol. 31, no. 10, 1997, pp. 1205-17.
Gottwald MD, Bainbridge JL, Dowling GA, et al. New pharmacotherapy for Parkinson's disease. Ann Pharmacother. 1997;31(10):1205-17.
Gottwald, M. D., Bainbridge, J. L., Dowling, G. A., Aminoff, M. J., & Alldredge, B. K. (1997). New pharmacotherapy for Parkinson's disease. The Annals of Pharmacotherapy, 31(10), 1205-17.
Gottwald MD, et al. New Pharmacotherapy for Parkinson's Disease. Ann Pharmacother. 1997;31(10):1205-17. PubMed PMID: 9337447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New pharmacotherapy for Parkinson's disease. AU - Gottwald,M D, AU - Bainbridge,J L, AU - Dowling,G A, AU - Aminoff,M J, AU - Alldredge,B K, PY - 1997/10/24/pubmed PY - 1997/10/24/medline PY - 1997/10/24/entrez SP - 1205 EP - 17 JF - The Annals of pharmacotherapy JO - Ann Pharmacother VL - 31 IS - 10 N2 - OBJECTIVE: To summarize the development, pharmacology, pharmacokinetics, efficacy, and safety of five investigational antiparkinsonian drugs that are in or have recently completed Phase III trials: three dopamine agonists, pramipexole, ropinirole, and cabergoline; and two catechol-O-methyltransferase (COMT) inhibitors, entacapone and tolcapone. The pathophysiology and the role of dopamine in Parkinson's disease are also reviewed. DATA SOURCES: A MEDLINE search of relevant English-language literature, clinical studies, abstracts, and review articles pertaining to Parkinson's disease was conducted. Manual searches of 1996/1997 meeting abstracts published by the American Academy of Neurology and the Movement Disorders Society were also performed. Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic data. STUDY SELECTION AND DATA EXTRACTION: Clinical trial investigations selected for inclusion were limited to human subjects. Interim analyses after 6 months for long-term clinical studies in progress were included. Pharmacokinetic data from animals were cited if human data were unavailable. Statistical analyses for all studies were evaluated. DATA SYNTHESIS: By selectivity targeting D2 receptors, the newer dopamine agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the introduction of levodopa and thus the occurrence of levodopa-induced dyskinesias. In addition, they are efficacious as adjunctive therapies in patients with advanced Parkinson's disease. Unlike the currently available dopamine agonists, pramipexole and ropinirole are non-ergot derivatives and do not cause skin inflammation, paresthesias, pulmonary infiltrates, or pleural effusion. The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of levodopa by preventing its peripheral catabolism and increasing the concentration of brain dopamine; thus, these agents may reduce the incidence of "wearing-off" effects associated with the short half-life of levodopa and the progression of Parkinson's disease. CONCLUSIONS: Interim 6-month analyses of pramipexole, ropinirole, and cabergoline for symptomatic treatment of early Parkinson's disease have shown these drugs to be efficacious and relatively well-tolerated when used as monotherapy. Their role in delaying the development of motor fluctuations and delaying the addition of levodopa is the subject of long-term clinical studies. In advanced stages of Parkinson's disease, these medications were also efficacious; however, the main adverse effects included dyskinesias, somnolence, and hallucinations. The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy in improving on-time in patients with stable disease. Tolcapone has also demonstrated efficacy in patients with motor fluctuations. Both drugs are relatively well-tolerated, with the exception of dyskinesias that require reduction of the levodopa dosage and occasional diarrhea. SN - 1060-0280 UR - https://www.unboundmedicine.com/medline/citation/9337447/New_pharmacotherapy_for_Parkinson's_disease_ L2 - https://journals.sagepub.com/doi/10.1177/106002809703101014?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -