The New Selective D2-dopamine Receptor Antagonist Raclopride—Pharmacokinetics, Safety and Tolerability in Healthy Males

Farde, Lars; Bahr, C von; Wahlén, A; Nilsson, Leif; Widman, M

doi:10.1097/00004850-198904000-00003

Cited by 16 publications

(13 citation statements)

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“…This is probably due to a short-lasting effect of raclopride on prolactin release via dopamine D2 receptor blockade. This has been demonstrated previously (3,19). We conclude that raclopride has an antipsychotic effect and produces few side effects; in the doses used in this study it did not appear to be as effective as haloperidol.…”

Section: Discussionsupporting

confidence: 81%

A double‐blind comparison of raclopride and haloperidol in the acute phase of schizophrenia

The British Isles Raclopride Study Group

1992

Acta Psychiatr Scand

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The British Isles Raclopride Study Group. A double-blind comparison of raclopride and haloperidol in the acute phase of schizophrenia.Acta Psychiatr Scand 1992: 86: 391-398. 0 Munksgaard 1992. This is the first comparative double-blind study of raclopride. Ninety-one patients with acute schizophrenia received either raclopride 2-8 mg twice daily or haloperidol 5-20 mg twice daily for 4 weeks. Both neuroleptics produced clinical improvements. There were no significant between-drug differences in overall efficacy measurements as assessed by the schizophrenia change sub-scale of the Comprehensive Psychopathological Rating Scale and the Krawiecka (Manchester) Rating Scale. Assessment by the Clinical Global Impression scale found haloperidol to be more effective. There were significantly fewer extrapyramidal symptoms with raclopride and a significantly lower incidence of acute dystonia. The results suggest that raclopride has an antipsychotic effect with a low incidence of extrapyramidal side effects.Raclopride((-)-( S)-3,5-dichloro-N-[ ( 1-ethyl-2-pyrrolidinyl) methyl]-2-hydroxy-6-methoxybenzamide-

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Section: Discussionsupporting

confidence: 81%

A double‐blind comparison of raclopride and haloperidol in the acute phase of schizophrenia

The British Isles Raclopride Study Group

1992

Acta Psychiatr Scand

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“…Farde et al (1989b) have suggested that raclopride is extensively metabolised after oral administration, as a result of the minor extent of renal excretion of unchanged drug. This conclusion is still valid taking into account 1 volunteer whose results deviated, with a possible interruption in the enterohepatic circula-tion due to diarrhoea_ This subject had a plasma clearance of 265 mlfmin (15.…”

Section: Discussionsupporting

confidence: 78%

“…A second peak after about 8 to IOh has been reported in a previous study (Farde et al 1989b). A second peak after about 8 to IOh has been reported in a previous study (Farde et al 1989b).…”

Section: Discussionsupporting

confidence: 78%

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Pharmacokinetics of Raclopride Formulations

Movin-Osswald

Nordström

Hammarlund‐Udenaes

et al. 1992

Clinical Pharmacokinetics

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The pharmacokinetic and pharmacodynamic properties of raclopride, a new antipsychotic, were investigated in 16 healthy men. Single 4 mg doses were administered as intravenous infusion, oral solution and 2 extended release (ER) formulations. Total plasma clearance was about 100 ml/min (6.0 L/h), of which renal clearance accounted for 0.2 ml/min, indicating extensive metabolism. The volume of distribution was 1.5 L/kg; mean absolute bioavailability was 65 to 67% following the oral solution and the ER formulations. A transient increase in plasma prolactin levels followed both the intravenous infusion and the oral solution. The ER formulations resulted in a lower increase, which appeared later. However, the area under the prolactin level curve was similar after administration of all dosage forms. The frequency and severity of the most commonly reported side effects (tiredness and restlessness) were higher after the intravenous infusion than after the ER capsules. These findings indicate that such capsules may be advantageous for clinical antipsychotic treatment with raclopride.

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“…Raclopride is reported to be rapidly metabolized after oral administration in humans (Farde et al, 1989), but the plasma metabolites were not identified. After intravenous injection of [ 11 C]raclopride, metabolites appeared slowly in plasma of cynomolgus monkey .…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of radiotracers in human plasma during positron emission tomography

Cumming

Yokoi

Chen

et al. 1999

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Many radiopharmaceuticals for positron emission tomography (PET) are substantially metabolized in peripheral organs. Pharmacological treatments intended to alter cerebral metabolism might also alter radiotracer metabolism, consequently altering the cerebral uptake. First-order rate constants for the metabolism of PET tracers can be calculated by a linear graphical method from the precursor and metabolite concentrations measured in plasma extracts fractionated by HPLC. We tested the effects of specific pharmacological challenges on the plasma kinetics of six tracers used for PET studies of neurotransmission. The rate of O-methylation of circulating [(18)F]fluorodopa, a tracer of dopa decarboxylase activity in brain, was unaffected by pretreatment with amantadine, an antagonist of glutamate receptors. [(11)C]Deprenyl, a tracer of monoamine oxidase activity, was rapidly metabolized to [(11)C]methamphetamine and polar metabolites in healthy volunteers. The net rate constant of this metabolism was three times higher in a group of subjects under treatment for epilepsy, consistent with induction of hepatic microsomal enzymes by antiepileptic drugs. [(11)C]Sch 23390, a ligand for dopamine D1 receptors, was rapidly metabolized to polar metabolites. The net rate constant of metabolism was unaffected by pretreatment with lorazepam. [(11)C]-(S)-Nicotine, a ligand for nicotinic receptors, was rapidly metabolized to [(11)C]-(S)-cotenine, which is less polar than the parent compound. Pretreatment with mazindol, a dopamine uptake inhibitor, was without effect on peripheral metabolism of [(11)C]-(S)-nicotine. [(11)C]WIN 35,428, a tropane derivative which labels dopamine uptake sites, was metabolized to a nonpolar metabolite, but so slowly that the rate constant of this process could not be calculated. [(11)C]Raclopride, a ligand for dopamine D2 receptors, was first metabolized to a nonpolar metabolite, which then yielded two hydrophilic metabolites. The initial metabolic step was substantially blocked by pretreatment with amphetamine, possibly indicative of competitive inhibition of microsomal oxidation. Together, these results indicate that the linear graphic method is useful for estimating the kinetics of the plasma metabolism of many widely used PET tracers. Drug-drug interactions were revealed in subjects treated with specific pharmacological agents prior to tracer administration.

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The New Selective D2-dopamine Receptor Antagonist Raclopride—Pharmacokinetics, Safety and Tolerability in Healthy Males

Cited by 16 publications

References 0 publications

A double‐blind comparison of raclopride and haloperidol in the acute phase of schizophrenia

A double‐blind comparison of raclopride and haloperidol in the acute phase of schizophrenia

Pharmacokinetics of Raclopride Formulations

Pharmacokinetics of radiotracers in human plasma during positron emission tomography

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