The Pharmacodynamics of Budipine on Central Neurotransmitter Systems

Offermeier, J; Rooyen, Johannes M. Van

doi:10.1007/978-3-642-95455-9_14

Cited by 6 publications

(4 citation statements)

References 13 publications

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“…Budipine N-oxide [4] was synthesized, and the agreement of spectroscopic and chromatographic data of metabolite M3 with the reference compound [4] corroborated the assigned structure. The LX fraction, metabolite M4, showed in the eH]-NMR spectra a p-substituted aromatic ring (doublets at 6.73 and 7.20 ppm) and residual aromatic signals identical with metabolite MI.…”

Section: Dose and Treatmentmentioning

confidence: 92%

“…Budipine N-oxide [4]. 100 mg of budipine, dissolved in 5 ml of methanol, was slowly mixed with 73 mg of m-chloroperbenzoic acid in 10 ml of methanol.…”

Section: Chromatographymentioning

confidence: 99%

“…Budipine, I-tert-bntyl-4,4-diphenylpiperidine 00, has shown marked antagonistic activity against tremor (1)(2)(3), enhances the effectiveness of L-DOPA treatment in Parkinson's disease, produces mood elevation and exhibits a peripheral sympathicotonic action (4).…”

Section: Introductionmentioning

confidence: 99%

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The metabolic fate of the anti-Parkinsonian drug budipine in rats

Caputo

Grosa

Ceruti

et al. 1991

European Journal of Drug Metabolism and Pharmacokinetics

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The metabolic fate of the anti-Parkinsonian drug budipine was studied in rats after oral administration. The presence of an aromatic hydroxylation product, metabolite M1, and its O-sulphate conjugate was confirmed. Three new minor metabolites, budipine N-oxide, metabolite M1 N-oxide and a secondary metabolite derived from M1 via hydroxylation of a methyl of the tert-butyl group, were isolated and identified in rat urine. The presence of a metabolite M1-glucuronic acid conjugate, was also established through different enzymatic treatments of the rat urine.

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Section: Dose and Treatmentmentioning

confidence: 92%

“…Budipine N-oxide [4]. 100 mg of budipine, dissolved in 5 ml of methanol, was slowly mixed with 73 mg of m-chloroperbenzoic acid in 10 ml of methanol.…”

Section: Chromatographymentioning

confidence: 99%

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The metabolic fate of the anti-Parkinsonian drug budipine in rats

Caputo

Grosa

Ceruti

et al. 1991

European Journal of Drug Metabolism and Pharmacokinetics

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“…Budipine does not bind to dopamine receptors (Przuntek and Stasch, 1985), it does not affect synaptosomal dopamine uptake and is devoid of stimulatory actions on KC1 evoked dopamine release (Offermeier and van Rooyen, 1985). In vivo activity of the dopamine inactivating enzyme monoamine oxidase B (MAO-B) is not blocked by budipine, although a reversible inhibition has been observed in vitro (Menge and Brand, 1982).…”

Section: Introductionmentioning

confidence: 97%

The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist

Klockgether

Jacobsen

Löschmann³

et al. 1993

J Neural Transm Gen Sect

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Budipine (1-t-butyl-4,4-diphenylpiperidine) is a novel antiparkinsonian agent. Its clinical efficacy has been proven in double-blind placebo-controlled trials. The mechanism of action of budipine, however, is unknown. Budipine selectively increased the threshold of N-methyl-D-aspartate (NMDA)-induced seizures in mice. Similar to known specific NMDA antagonist, budipine depressed polysynaptic spinal reflexes in mice, but had no consistent effect on spinal monosynaptic reflexes. In receptor binding experiments, budipine displaced thienylcyclohexylpiperidyl-3,4-[3H]-(n) ([3H]-TCP) from its binding site with an IC50 of 36 microM suggesting that budopine acts as a non-competitive NMDA antagonist with moderate receptor affinity. It is concluded that the newly discovered NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity. Our findings are additional evidence for the hypothesis that NMDA antagonists may be useful in the treatment of Parkinson's disease (PD).

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The antiparkinsonian drug budipine stimulates the activity of aromatic L-amino acid decarboxylase and enhances L-DOPA-induced dopamine release in rat substantia nigra

Biggs¹,

Fisher²,

Starr³

1998

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The present study examined the effects of the antiparkinsonian drug budipine on dopamine synthesis and release from L-DOPA in the substantia nigra of reserpine-treated rats. Budipine (at 100 microM, but not 10 microM) applied by reverse dialysis to the nigra caused a small and significant rise in dopamine recovery in normal rats, but not in rats pretreated with reserpine (4 mg/kg i.p. for 18 hours) and alpha-methyl-p-tyrosine (alpha-MPT; 200 mg/kg i.p. for 1 hour to limit dopamine synthesis to L-DOPA). L-DOPA applied to the nigra by reverse dialysis in reserpine + alpha-MPT-treated rats, increased the recovery of dopamine when applied at 5 or 10 microM, but not at 2 microM. Coadministration of budipine (10 microM) significantly enhanced L-DOPA-induced dopamine (and DOPAC) release with 5 microM L-DOPA, but not with 2 or 10 microM L-DOPA. This potentiation was even more pronounced when the budipine concentration was raised to 100 microM (equivalent to approximately 10 microM extracellularly). Pretreating rats with budipine (5, 12.5, or 20 mg/kg i.p.) for 1 hour significantly raised the activity of the enzyme L-aromatic amino acid decarboxylase in the striata and nigras of intact rats, as well as in rats pretreated with reserpine alone (5 mg/kg i.p.), without altering tissue levels of dopamine or its metabolites. It is suggested that the beneficial effects of budipine, when used as an adjunct to L-DOPA therapy of Parkinson's disease, may be due to an increase in the bioconversion of L-DOPA with a consequent rise in synaptic dopamine. These actions of budipine may be related to its weak NMDA receptor antagonist property.

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The Pharmacodynamics of Budipine on Central Neurotransmitter Systems

Cited by 6 publications

References 13 publications

The metabolic fate of the anti-Parkinsonian drug budipine in rats

The metabolic fate of the anti-Parkinsonian drug budipine in rats

The antiparkinsonian agent budipine is an N-methyl-D-aspartate antagonist

The antiparkinsonian drug budipine stimulates the activity of aromatic L-amino acid decarboxylase and enhances L-DOPA-induced dopamine release in rat substantia nigra

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