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Titolo:
Comparative pharmacological study of ropinirole (SKF-101468) and its metabolites in rats
Autore:
Reavill, C; Boyfield, I; Coldwell, M; Nelson, P;
Indirizzi:
SmithKline Beecham Pharmaceut, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AW ssex, England
Titolo Testata:
JOURNAL OF PHARMACY AND PHARMACOLOGY
fascicolo: 9, volume: 52, anno: 2000,
pagine: 1129 - 1135
SICI:
0022-3573(200009)52:9<1129:CPSOR(>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
EARLY PARKINSONS-DISEASE; HAMSTER OVARY CELLS; DOPAMINE-D2 AGONIST; HUMAN D-2(LONG); HUMAN FOREBRAIN; RECEPTORS; D-3; D3; 6-HYDROXYDOPAMINE; BROMOCRIPTINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Reavill, C SmithKline Beecham Pharmaceut, New Frontiers Sci Pk,3rd Ave, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut New Frontiers Sci Pk,3rd Ave Harlow Essex England CM19 5AW
Citazione:
C. Reavill et al., "Comparative pharmacological study of ropinirole (SKF-101468) and its metabolites in rats", J PHARM PHA, 52(9), 2000, pp. 1129-1135

Abstract

The dopamine receptor agonist ropinirole (SKF-101468) is used to treat Parkinson's disease. Ropinirole is metabolized by two routes to a series of different metabolites although the predominant pathway is species-dependent. It is unknown whether any of the metabolites contribute to its antiparkinsonian activity and whether D-3 or D-2 receptor agonist activity plays a preferential role. Therefore ropinirole and its primary metabolites, SKF-104557, SKF-97930 and SKF-96990, and the rat metabolite, SKF-89124 were tested inthe 6-hydroxydopamine lesion model of Parkinson's disease. SKF-89124 and SKF-96990 were also assayed in radioligand binding and microphysiometer functional assays at cloned human dopamine D-2 and D-3. Ropinirole and SKF-89124 were equipotent in-vivo, and produced dose-related increases in circling at 0.05-0.8 mg kg(-1), s.c. (ropinirole) and 0.05-0.75 mg kg(-1), s.c. (SKF-89124). Neither SKF-96990 or SKF-97930, at doses up to 15 mg kg-l, increased the circling rate. Some circling was observed with 15 mg kg-l SKF-104557 but the response was less than half that produced by ropinirole (0.8 mg kg(-1)). SKF-104557 was 150-fold less potent than ropinirole. SKF-89124 possessed-30-fold higher affinity for D-3 over D-2 receptors in radioligand binding studies, but was not selective in the functional microphysiometer assay. SKF-96990 was 10-fold selective for D-3 over D-2 receptors in the radioligand binding assay. Ropinirole and SKF-104557 are 20-fold selective for D-3 over D-2 receptors in radioligand binding assays whereas in microphysiometry, selectivity is 10-fold. SKF-97930 is inactive in radioligand binding and microphysiometer assays. Primary metabolites of ropinirole did not contribute significantly to its activity in this model of Parkinson's disease. The lack of dopamine D-3/D-2receptor selectivity for ropinirole rules out the possibility of attributing the degree of either D-2 or D-3 receptor activity to the behavioural efficacy of ropinirole.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/01/20 alle ore 01:44:33