Single oral dose pharmacokinetics of tiapride in patients with Huntington's disease

Norman, Trevor R.; Chiu, Edmond; James, R H; Gregory, Margaret S.

doi:10.1007/bf02455992

Cited by 12 publications

(8 citation statements)

References 11 publications

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“…Immediately after this session, the dopaminergic antagonist tiapride was administered orally in a single dose of 100 mg. Control participants received an identical-looking placebo. One hundred and twenty minutes after administration of the drug/placebo, in accordance with the pharmacokinetic profile of tiapride with peak plasma concentrations achieved around this time point (Rey et al, 1982 ; Norman et al, 1987 ), the second fMRI session was performed, which comprised the extinction learning phase and the extinction recall phase. Tiapride is a selective antagonist of D2 and D3 dopamine receptors (Dose and Lange, 2000 ), which has previously been shown to impair motor learning in humans (Lissek et al, 2014 ), as well as taste (Mediavilla et al, 2012 ) and place (Hurtado et al, 2014 ) aversion learning in rats.…”

Section: Methodsmentioning

confidence: 99%

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

Lissek

Glaubitz

Wolf

et al. 2015

Front. Behav. Neurosci.

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Renewal describes the recovery of an extinguished response if recall is tested in a context different from the extinction context. Behavioral studies demonstrated that attention to relevant context strengthens renewal. Neurotransmitters mediating attention and learning such as the dopaminergic (DA) system presumably modulate extinction learning and renewal. However, the role of DA for non-fear-based extinction learning and renewal in humans has not yet been investigated. This fMRI study investigated effects of DA-antagonism upon context-related extinction in a predictive learning task in which extinction occurred either in a novel (ABA) or an unchanged (AAA) context. The tiapride-treated group (TIA) showed significantly impaired ABA extinction learning and a significant within-group difference between ABA and AAA extinction, compared to placebo (PLAC). Groups did not differ in their level of ABA renewal. In ABA extinction, TIA showed reduced activation in dlPFC and OFC, hippocampus, and temporal regions. Across groups, activation in PFC and hippocampus correlated negatively with ABA extinction errors. Results suggest that in context-related extinction learning DA in PFC and hippocampus is involved in readjusting the cue-outcome relationship in the presence of a novel context. However, relating context to the appropriate association during recall does not appear to rely exclusively on DA signaling.

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Section: Methodsmentioning

confidence: 99%

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

Lissek

Glaubitz

Wolf

et al. 2015

Front. Behav. Neurosci.

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“…There was very little difference in tiapride elimination parameters between volunteers and patients (table III), with the exception of a decreased percentage of :he dose eliminated in urine in the patient groups and a prolonged elimination halflife (t'l2,3) in the study of Norman et al (1987). These latter investigators ascribed this to the mean age of the patient group being about double that of the volunteers in other studies, and possibly as a result of the disease process.…”

Section: Eliminationmentioning

confidence: 81%

“…The methods used for measuring concentrations of tiapride and its metabolites in body fluids include gas chromatography (Kamizono et al 1991), high performance liquid chromatography (Norman et al 1986(Norman et al , 1987Rey et al 1982a, b) and radioactivity from [3H]tiapride as measured by liquid scintillation (Strolin-Benedetti et al 1978).…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Tiapride

Steele¹,

Faulds²,

Sorkin³

1993

Drugs & Aging

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Tiapride is a substituted benzamide derivative with selective dopamine D2-receptor antagonist properties which appears to have preferential affinity for extrastriatal dopamine receptors. Animal and clinical studies show that tiapride has anxiolytic properties but the mechanism of action is uncertain. Results from limited studies indicate that the clinical efficacy of tiapride in the treatment of agitation, aggressiveness, anxiety and sleep disorders in the elderly appears superior to that of placebo, chlorpromazine, lorazepam and meprobamate. Tiapride also exerts a beneficial effect on vigilance and alertness in elderly patients and causes less sedation than chlorpromazine. Tiapride is well tolerated at the dosages recommended for elderly patients. Further well designed comparative studies with newer drugs are needed to determine the relative place of tiapride in the treatment of geriatric agitation, and such studies should also address the quality-of-life benefits for the patient. Additional clinical experience to determine the efficacy of tiapride in elderly patients with more than one disease condition, receiving concomitant medications, and/or with renal impairment is also required. However, despite these current limitations, tiapride may have potentially important applications in this difficult area of clinical medicine.

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“…Then, participants assigned to the experimental group received a single oral dose of 100 mg of the DA-antagonist tiapride, while participants assigned to the control group received an identical-looking placebo. 2 h after administration of the drug/placebo, in accordance with the pharmacokinetic profile of tiapride with peak plasma concentration achieved around this time point (Rey et al, 1982; Norman et al, 1987), the experimental procedure started with the pre-training assessment of CE, followed by training and performance of the motor sequence task in the MRI scanner. Afterwards, CE post-training was assessed.…”

Section: Methodsmentioning

confidence: 98%

Opposing effects of dopamine antagonism in a motor sequence taskâ€”tiapride increases cortical excitability and impairs motor learning

Lissek

Vallana

Schlaffke

et al. 2014

Front. Behav. Neurosci.

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The dopaminergic system is involved in learning and participates in the modulation of cortical excitability (CE). CE has been suggested as a marker of learning and use-dependent plasticity. However, results from separate studies on either motor CE or motor learning challenge this notion, suggesting opposing effects of dopaminergic modulation upon these parameters: while agonists decrease and antagonists increase CE, motor learning is enhanced by agonists and disturbed by antagonists. To examine whether this discrepancy persists when complex motor learning and motor CE are measured in the same experimental setup, we investigated the effects of dopaminergic (DA) antagonism upon both parameters and upon task-associated brain activation. Our results demonstrate that DA-antagonism has opposing effects upon motor CE and motor sequence learning. Tiapride did not alter baseline CE, but increased CE post training of a complex motor sequence while simultaneously impairing motor learning. Moreover, tiapride reduced activation in several brain regions associated with motor sequence performance, i.e., dorsolateral PFC (dlPFC), supplementary motor area (SMA), Broca's area, cingulate and caudate body. Blood-oxygenation-level-dependent (BOLD) intensity in anterior cingulate and caudate body, but not CE, correlated with performance across groups. In summary, our results do not support a concept of CE as a general marker of motor learning, since they demonstrate that a straightforward relation of increased CE and higher learning success does not apply to all instances of motor learning. At least for complex motor tasks that recruit a network of brain regions outside motor cortex, CE in primary motor cortex is probably no central determinant for learning success.

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Single oral dose pharmacokinetics of tiapride in patients with Huntington's disease

Cited by 12 publications

References 11 publications

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

Tiapride

Opposing effects of dopamine antagonism in a motor sequence taskâ€”tiapride increases cortical excitability and impairs motor learning

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