Preliminary investigation of the metabolism of piribedil (ET 495); a new central dopaminergic agonist and potential anti-parkinson agent

Jenner, Peter; Taylor, A. R.; Campbell, David B.

doi:10.1111/j.2042-7158.1973.tb10060.x

Cited by 56 publications

(10 citation statements)

References 3 publications

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“…The apparent actions of the drug on a D 1 ‐mediated system suggest activity on this receptor system. Indeed, a metabolite of piribedil, namely S 584, can act as a D 1 agonist, because it stimulates dopamine‐sensitive adenylate cyclase 89–91. However, it has not been thought that S 584 has a sufficiently high affinity for D 1 receptors or that it is present in brain in sufficient amounts to contribute to the pharmacological actions of piribedil 92, 93.…”

Section: Discussionmentioning

confidence: 99%

Repeated administration of piribedil induces less dyskinesia than L‐dopa in MPTP‐treated common marmosets: A behavioural and biochemical investigation

et al. 2002

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Piribedil ([1-(3,4-methylenedioxybenzyl)-4-(2-pyrimidinyl)piperazine]; S 4200) is a dopamine agonist with equal affinity for D(2)/D(3) dopamine receptors effective in treating Parkinson's disease as monotherapy or as an adjunct to levodopa (L-dopa). However, its ability to prime basal ganglia for the appearance of dyskinesia is unknown. We now report on the ability of repeated administration of piribedil to induce dyskinesia in drug naïve 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -lesioned common marmosets compared with L-dopa and its actions on the direct and indirect striatal outflow pathways. Administration of piribedil (4.0-5.0 mg/kg orally) or L-dopa (12.5 mg/kg orally plus carbidopa 12.5 mg/kg orally twice daily) produced equivalent increases in locomotor activity and reversal of motor deficits over a 28-day study period. Administration of L-dopa resulted in the progressive development of marked dyskinesia over the period of study. In contrast, administration of piribedil produced a significantly lower degree and intensity of dyskinesia. Surprisingly, piribedil caused an increase in vigilance and alertness compared to L-dopa, which may relate to the recently discovered alpha(2)-noradrenergic antagonist properties of piribedil. The behavioural differences between piribedil and L-dopa are reflected in the biochemical changes associated with the direct striatal output pathway. Administration of L-dopa or piribedil did not reverse the MPTP-induced up-regulation of preproenkephalin A mRNA in rostral or caudal areas of the putamen or caudate nucleus. In contrast, administration of either piribedil or L-dopa reversed the downregulation of preprotachykinin mRNA induced by MPTP in rostral and caudal striatum. L-dopa, but not Piribedil, reversed the decrease in preproenkephalin B mRNA produced by MPTP treatment.

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Section: Discussionmentioning

confidence: 99%

Repeated administration of piribedil induces less dyskinesia than L‐dopa in MPTP‐treated common marmosets: A behavioural and biochemical investigation

et al. 2002

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“…Excretion of unchanged drug was negligible (about 0.1% of the dose), as expected, whereas almost 16% of the administered dose was excreted as metabolites (MI, M2, their glucuronide and/or sulfate conjugated, and MJ). It should be stressed that this figure is a minimum since besides a number of unidentified acid metabolites (2), there may well be some other basic metabolites that were not measured in this study. Two new metabolites have been recently identified in man: trihydroxylated piribedil produced by demethylation of the methylene dioxy-phenyl bridge associated with a-hydroxylation of the pyrimidine ring; and methoxydihydroxylated piribedil derived from acetylation of a hydroxy function of the trihydroxylated piribedil (11).…”

Section: Specimen (Ljg1ml) M] M2 Mjmentioning

confidence: 85%

Solid-phase extraction of piribedil and its metabolites from plasma and urine without and after deconjugation, by high performance liquid chromatography

Sarati

Caccia

1992

European Journal of Drug Metabolism and Pharmacokinetics

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A new high performance liquid chromatographic procedure has been developed for the simultaneous quantification of piribedil (PD) and its three main basic metabolites in rat plasma and urine, without and after hydrolysis. The procedure relies on isolation of the compounds from plasma and urine constituents using the Sep-Pak C18 cartridge, with satisfactory recovery and specificity, and resolution by acetonitrile gradient elution on a C18 reversed phase column coupled to a UV detector monitored at 240 nm. The assay was linear over a wide range of concentrations for all compounds in both body fluids with mean within-day and day-to-day coefficient of variation (CV) and relative error (RE) generally below 10%. Plasma concentrations of PD and its metabolites at selected intervals and urinary recoveries of all compounds before and after enzymatic hydrolysis are presented.

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“…Determination of piribedil in pharmaceutical formulations by micellar electrokinetic capillary chromatography Several analytical methods for the determination of P have been reported, including spectrophotometry [3,4], high-performance liquid chromatography [5,6], gas chromatography [7], gas chromatography-mass spectrometry [8], ion-selective electrodes [9] and voltammetry [10]. There is no capillary electrophoresis method for the determination of P.…”

Section: Ceren Yardımcı · İncilay Süslü · Nuran öZaltınmentioning

confidence: 99%

Determination of piribedil in pharmaceutical formulations by micellar electrokinetic capillary chromatography

Yardımcı

Süslü

Özaltı́n

2004

Analytical and Bioanalytical Chemistry

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A fast and simple micellar electrokinetic capillary chromatographic method was developed for the analysis of piribedil in pharmaceutical formulations. The effects of buffer concentration, buffer pH, sodium dodecyl sulphate (SDS) concentration, organic modifier, applied voltage and injection time were investigated. Optimum results were obtained with a 50 mM borate buffer at pH 8.0 containing 50 mM SDS by using a fused silica capillary (50 microm internal diameter, 72 cm effective length). The sample was injected hydrodynamically for 4 s at 50 mbar pressure and the applied voltage was +30 kV. The detection wavelength was set at 205 nm. Diflunisal was used as an internal standard. The analysis was performed at 25 degrees C and the total run time was 14 min. The method was suitably validated with respect to linearity range, limit of detection and quantification, precision, accuracy, specificity and robustness. The linear calibration range was 5-100 microg mL(-1) and the limit of detection was determined as 1 microg mL(-1). The method developed was successfully applied to the determination of piribedil in pharmaceutical formulations. The results were compared with a spectrophotometric method reported in the literature and no significant difference was found statistically.

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Preliminary investigation of the metabolism of piribedil (ET 495); a new central dopaminergic agonist and potential anti-parkinson agent

Cited by 56 publications

References 3 publications

Repeated administration of piribedil induces less dyskinesia than L‐dopa in MPTP‐treated common marmosets: A behavioural and biochemical investigation

Repeated administration of piribedil induces less dyskinesia than L‐dopa in MPTP‐treated common marmosets: A behavioural and biochemical investigation

Solid-phase extraction of piribedil and its metabolites from plasma and urine without and after deconjugation, by high performance liquid chromatography

Determination of piribedil in pharmaceutical formulations by micellar electrokinetic capillary chromatography

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