Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Mechanisms of action of pramipexole: Putative neuroprotective effects
Autore:
Bennett, JP; Carvey, PM; Hinds, TR; Johnson, RD; Le, WD; Phillips, W; Sethy, VH; Vincenzi, FF; Youdim, MBH;
Indirizzi:
Univ Virginia, Hlth Sci Ctr, Dept Neurol, Charlottesville, VA 22908 USA Univ Virginia Charlottesville VA USA 22908 Charlottesville, VA 22908 USA Rush Presbyterian St Lukes Med Ctr, Dept Pharmacol, Chicago, IL 60612 USA Rush Presbyterian St Lukes Med Ctr Chicago IL USA 60612 ago, IL 60612 USA Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA Univ Washington Seattle WA USA 98195 ept Pharmacol, Seattle, WA 98195 USA Guys Hosp, Guys Kings & St Thomass Sch Med, Dept Anat, London SE1 1UL, England Guys Hosp London England SE1 1UL Med, Dept Anat, London SE1 1UL, England Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA Baylor Coll Med Houston TX USA 77030 , Dept Neurol, Houston, TX 77030 USA Addenbrookes Hosp, Dept Neurol, Cambridge CB2 2SE, England Addenbrookes Hosp Cambridge England CB2 2SE , Cambridge CB2 2SE, England Technion Israel Inst Technol, Fac Med, Eve Topf & Natl Parkinson Fdn Ctr Excellence Neur, IL-31096 Haifa, Israel Technion Israel Inst Technol HaifaIsrael IL-31096 L-31096 Haifa, Israel Technion Israel Inst Technol, Fac Med, Dept Pharmacol, IL-31096 Haifa, Israel Technion Israel Inst Technol Haifa Israel IL-31096 L-31096 Haifa, Israel
Titolo Testata:
REVIEWS IN CONTEMPORARY PHARMACOTHERAPY
fascicolo: 1-2, volume: 12, anno: 2001,
pagine: 33 - 57
SICI:
0954-8602(2001)12:1-2<33:MOAOPP>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSIENT FOREBRAIN ISCHEMIA; INHIBITS LIPID-PEROXIDATION; MITOCHONDRIAL COMPLEX-I; IRON CHELATOR DESFERRIOXAMINE; IDIOPATHIC PARKINSONS-DISEASE; CENTRAL-NERVOUS-SYSTEM; FREE-RADICAL FORMATION; NF-KAPPA-B; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
227
Recensione:
Indirizzi per estratti:
Indirizzo: Bennett, JP Box 15, Carnforth LA6 1HW, England Box 15 Carnforth England LA6 1HW Carnforth LA6 1HW, England
Citazione:
J.P. Bennett et al., "Mechanisms of action of pramipexole: Putative neuroprotective effects", REV CONT PH, 12(1-2), 2001, pp. 33-57

Abstract

The neurodegenerative mechanisms involved in the aetiopathogenesis of Parkinson's disease have yet to be fully elucidated. It seems likely, however, that a major role is played by oxidative stress, related to the generation of free radicals associated with dopamine metabolism and loss of mitochondrial electron transport function. Neurotoxins, arising exogenously and/or endogenously, may also be involved. Evidence that pramipexole, a dopamine D-3-preferring agonist, possesses a neuroprotective potential comes from a number of directions. In studies conducted in vivo, pramipexole protects dopaminergic neurones against the effects of transient forebrain ischaemia, and against the neurotoxic effects of methamphetamine, 3-acetylpyridine, 6-hydroxydopamine and MPTP. In in vitro studies using cultures of rat mesencephalic, human neuroblastoma, rat mesencephalic/murine neuroblastoma-glioma hybrid, or rat cerebellar granule cells, pramipexole has been shown to attenuate the neurotoxic effects of dopamine and the L form of 3,4-dihydroxyphenylalanine (L-DOPA) in neuronal cell culture, as well as of MPP+, these effectsapparently being linked to pramipexole's antioxidant, free-radical scavenging actions. It has also been demonstrated that D-3 receptor stimulation may be a necessary element in at least part of the neuroprotective action exerted by pramipexole, whilst other studies suggest that pramipexole may enhance trophic activity in dopaminergic cells. It seems likely that the neuroprotective actions of pramipexole involve these different mechanisms (and possibly others) acting in concert. In contrast to the substantial evidence from laboratory studies that pramipexole is able to exert marked neuroprotective effects on dopaminergic neurones, it is not yet clear that such effects form an important part of the therapeutic action of pramipexole when it is used clinically in the treatment of Parkinson's disease. Recent evidence from single photon emission computed tomography (SPECT) imaging studies hasrevealed a trend towards a reduction in dopaminergic neurodegeneration in patients with early Parkinson's disease treated with pramipexole, relative to effects seen in patients treated for the same period of time with carbidopa/L-DOPA; after approximately 2 years the trend did not attain statistical significance, but patients are being followed up for a further 2 years. Further work is required to establish whether, and to what extent, the neuroprotective actions of pramipexole seen in laboratory-based studies translate into the protection and preservation of nigrostriatal dopaminergic neurones in parkinsonian patients.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:56:01