Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Mechanisms of action of pramipexole: Effects on receptors
Autore:
Dziedzicka-Wasylewska, M; Ferrari, F; Johnson, RD; Mierau, J; Rogoz, Z; Skuza, G; Sokoloff, P;
Indirizzi:
Polish Acad Sci, Inst Pharmacol, PL-31343 Krakow, Poland Polish Acad Sci Krakow Poland PL-31343 harmacol, PL-31343 Krakow, Poland Univ Modena, Div Pharmacol, Dept Biomed Sci, I-41100 Modena, Italy Univ Modena Modena Italy I-41100 Dept Biomed Sci, I-41100 Modena, Italy 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 Boehringer Ingelheim Pharma KG, Dept CNS Res, D-55216 Ingelheim, Germany Boehringer Ingelheim Pharma KG Ingelheim Germany D-55216 elheim, Germany INSERM, Ctr Paul Broca, Unite Neurobiol & Pharmacol Mol, F-75014 Paris, France INSERM Paris France F-75014 obiol & Pharmacol Mol, F-75014 Paris, France
Titolo Testata:
REVIEWS IN CONTEMPORARY PHARMACOTHERAPY
fascicolo: 1-2, volume: 12, anno: 2001,
pagine: 1 - 31
SICI:
0954-8602(2001)12:1-2<1:MOAOPE>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINE D-3 RECEPTOR; B-HT 920; INSITU HYBRIDIZATION HISTOCHEMISTRY; DISCRIMINATIVE STIMULUS PROPERTIES; SPONTANEOUSLY HYPERTENSIVE RAT; STRESS-INDUCED ANHEDONIA; PLASMA PROLACTIN LEVELS; INACTIVE MALE-RATS; PARKINSONS-DISEASE; D2-DOPAMINE RECEPTOR;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
318
Recensione:
Indirizzi per estratti:
Indirizzo: Dziedzicka-Wasylewska, M Box 15, Carnforth LA6 1HW, England Box 15 Carnforth England LA6 1HW 6 1HW, England
Citazione:
M. Dziedzicka-Wasylewska et al., "Mechanisms of action of pramipexole: Effects on receptors", REV CONT PH, 12(1-2), 2001, pp. 1-31

Abstract

Pramipexole, a tetrahydrobenzothiazole compound, has selective affinity for dopamine receptors of the D2 subfamily, with a 7-10-fold greater affinityfor D-3 than for D-2 receptor subtypes; affinity for the D-4 receptor subtype is 17-fold less than for D-3 receptors. The available experimental evidence suggests that, in intact normofunctional dopaminergic systems, pramipexole exerts its primary effects on presynaptic dopamine autoreceptors, probably of both D-2 and D-3 subtypes, as a result of which it suppresses the synthesis and synaptic release of dopamine; effects on postsynaptic receptors are elicited only at higher dose levels and with substantially longer latencies than are needed for presynaptic autoreceptor stimulation. However, in dopaminergic systems in which dopamine release is reduced, as a result ofpresynaptic neurone degeneration or destruction, or by other means, postsynaptic dopamine D-2 and D-3 receptors are much more readily stimulated by pramipexole. These receptor effects of pramipexole may be linked to its established or putative therapeutic effects in conditions related to reduced levels of dopamine release. Thus, it is proposed that, in Parkinson's disease, pramipexole readjusts the balance between direct and indirect striatopallidal outflow pathways which, acting together, modulate the inhibition/facilitation of motor activity; this occurs as a result of the stimulation of both D-2 and D-3 postsynaptic receptors in dopamine depleted circuits. Pramipexole has been reported to have beneficial effects against depression, an action which seems likely to reflect pramipexole-induced stimulation of postsynaptic dopamine D2 receptors; this same effect in frontal cortical regions may reduce the negative symptoms of schizophrenia. Pramipexole may also exert therapeutic effects in certain states of dopaminergic dysfunction which do not involve reduced levels of dopamine. The suppression of dopamine release in mesolimbic regions, resulting from the stimulation by pramipexole of presynaptic dopamine D2 autoreceptors, may lead to positive therapeutic effects in schizophrenia and anxiety disorders. Pramipexole may find some clinical role as an adjunct to treatment programmes aimed at reducing cocaine abuse. Further elucidation of the effects which pramipexole is able to elicit at the level of dopamine receptors in different brain regions will notonly provide valuable insights into the role of dopaminergic mechanisms ina range of neuropsychiatric dysfunctions, but will lead to the further refinement of effective therapies for such conditions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 14:40:33