Occupancy of dopamine D1, D2 and serotonin2A receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol

Reimold, Matthias; Solbach, Christoph; Noda, S.; Schaefer, Jacques-Emmanuel; Bartels, M.; Beneke, Manfred; Machulla, Hans-Juergen; Bares, Roland; Gläser, Thomas; Wormstall, H.

doi:10.1007/s00213-006-0611-0

Cited by 51 publications

(33 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are unable, therefore, to draw conclusions regarding the sub-type of DA receptors mediating the observed effects. Furthermore, as flupentixol is also known to bind with high affinity to other receptors, including serotonin (2A) and adrenergic (a1) receptors (Reimold et al, 2007;Testa et al, 1989) we cannot rule out the possibility that antagonism of these other neurotransmitter systems contributes to the behavioral effects of flupentixol reported here and elsewhere.…”

Section: Discussionmentioning

confidence: 77%

Dopamine Receptor Blockade Attenuates the General Incentive Motivational Effects of Noncontingently Delivered Rewards and Reward-Paired Cues Without Affecting Their Ability to Bias Action Selection

Ostlund¹,

Maidment²

2011

Neuropsychopharmacol

View full text Add to dashboard Cite

Environmental cues affect our behavior in a variety of ways. Despite playing an invaluable role in guiding our daily activities, such cues also appear to trigger the harmful, compulsive behaviors that characterize addiction and other disorders of behavioral control. In instrumental conditioning, rewards and reward-paired cues bias action selection and invigorate reward-seeking behaviors, and appear to do so through distinct neurobehavioral processes. Although reward-paired cues are known to invigorate performance through a dopamine-dependent incentive motivational process, it is not known if dopamine also mediates the influence of rewards and rewardpaired cues over action selection. The current study contrasted the effects of systemic administration of the nonspecific dopamine receptor antagonist flupentixol on response invigoration and action bias in Pavlovian-instrumental transfer, a test of cue-elicited responding, and in instrumental reinstatement, a test of noncontingent reward-elicited responding. Hungry rats were trained on two different stimulus-outcome relationships (eg, tone-grain pellets and noise-sucrose solution) and two different action-outcome relationships (eg, left press-grain and right press-sucrose). At test, we found that flupentixol pretreatment blocked the response invigoration generated by the cues but spared their ability to bias action selection to favor the action whose outcome was signaled by the cue being presented. The response-biasing influence of noncontingent reward deliveries was also unaffected by flupentixol. Interestingly, although flupentixol had a modest effect on the immediate response invigoration produced by those rewards, it was particularly potent in countering the lingering enhancement of responding produced by multiple reward deliveries. These findings indicate that dopamine mediates the general incentive motivational effects of noncontingent rewards and reward-paired cues but does not support their ability to bias action selection.

show abstract

Section: Discussionmentioning

confidence: 77%

Dopamine Receptor Blockade Attenuates the General Incentive Motivational Effects of Noncontingently Delivered Rewards and Reward-Paired Cues Without Affecting Their Ability to Bias Action Selection

Ostlund¹,

Maidment²

2011

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…An analysis of three-dimensional structures and molecular electrostatic potentials confirms the higher receptor affinities of cis-flupentixol in comparison to the trans-isomer (Sylte and Dahl 1991). In the already mentioned PET study with flupentixol, the presented drug plasma concentrations appear to be those of the sum of cis-and trans-flupentixol, as the standard analytical technique used by MDS Pharma Services (Fehraltorf, Switzerland) was not developed for the separation of these isomers (Reimold et al 2007; and Petra Struwe, Celerion, Fehraltdorf, personal communication).Recently, the AGNP-TDM group (Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie) ) recommended published updated consensus guidelines for therapeutic drug monitoring in psychiatry: The therapeutic reference range (recommended plasma drug concentration) for the antipsychotic drug flupentixol (flupenthixol) was given as 1-10 ng/ml. This range is related to the sum of the cis-and the trans-isomers concentrations, and the recommended range is mainly based on 2 studies (Reimold et al 2007;Balant-Gorgia et al 1985).…”

mentioning

confidence: 99%

“…Such studies have been carried out for many antipsychotics, the binding of which to central dopamine D2 receptors can be observed with PET (Grunder et al 2011). A study showed a 50-70 % D2-receptor occupancy by therapeutic doses (4-10 mg/day; 5.7±1.4 mg/day [mean ± SD]) of the antipsychotic drug flupentixol, which reportedly lead to flupentixol plasma concentrations between 0 and 6 ng/ml (1.47±0.97 ng/ml) after oral administration of this drug to 13 patients (Reimold et al 2007). Flupentixol is available as a 1:1 mixture of the geometric isomers cis-and trans-isomers (Z-and E-isomers, respectively) for oral administration, while the depot preparation flupentixol decanoate contains only cis-flupentixol.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…This range is related to the sum of the cis-and the trans-isomers concentrations, and the recommended range is mainly based on 2 studies (Reimold et al 2007;Balant-Gorgia et al 1985). The question arises whether after analysis of the literature, which considers pharmacological and pharmacokinetic differences between the cis-and trans-isomers of flupentixol, the recommended plasma concentration range of flupentixol may still be considered as valid.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Flupentixol: relevance of stereoselective therapeutic drug monitoring

Baumann

Kirchherr²,

Berney

et al. 2012

Psychopharmacology

View full text Add to dashboard Cite

Positron emission tomography (PET) provides important information in studies centered on the drug plasma concentrations-clinical effectiveness relationship, as it directly allows measuring of drug binding to pharmacologically relevant receptors in the brain. Such studies have been carried out for many antipsychotics, the binding of which to central dopamine D2 receptors can be observed with PET (Grunder et al. 2011). A study showed a 50-70 % D2-receptor occupancy by therapeutic doses (4-10 mg/day; 5.7±1.4 mg/day [mean ± SD]) of the antipsychotic drug flupentixol, which reportedly lead to flupentixol plasma concentrations between 0 and 6 ng/ml (1.47±0.97 ng/ml) after oral administration of this drug to 13 patients (Reimold et al. 2007). Flupentixol is available as a 1:1 mixture of the geometric isomers cis-and trans-isomers (Z-and E-isomers, respectively) for oral administration, while the depot preparation flupentixol decanoate contains only cis-flupentixol. Only cis-flupentixol is considered to be pharmacologically active with regard to its affinity for dopamine (and serotonin) receptors, as also shown in clinical studies in which clinical efficacy of cis-flupentixol (α-flupentixol; Z-flupentixol) was found to be superior to that of trans-flupentixol (β-flupentixol; E-flupentixol) (Johnstone et al. 1978). An analysis of three-dimensional structures and molecular electrostatic potentials confirms the higher receptor affinities of cis-flupentixol in comparison to the trans-isomer (Sylte and Dahl 1991). In the already mentioned PET study with flupentixol, the presented drug plasma concentrations appear to be those of the sum of cis-and trans-flupentixol, as the standard analytical technique used by MDS Pharma Services (Fehraltorf, Switzerland) was not developed for the separation of these isomers (Reimold et al. 2007; and Petra Struwe, Celerion, Fehraltdorf, personal communication).Recently, the AGNP-TDM group (Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie) ) recommended published updated consensus guidelines for therapeutic drug monitoring in psychiatry: The therapeutic reference range (recommended plasma drug concentration) for the antipsychotic drug flupentixol (flupenthixol) was given as 1-10 ng/ml. This range is related to the sum of the cis-and the trans-isomers concentrations, and the recommended range is mainly based on 2 studies (Reimold et al. 2007;Balant-Gorgia et al. 1985). The question arises whether after analysis of the literature, which considers pharmacological and pharmacokinetic differences between the cis-and trans-isomers of flupentixol, the recommended plasma concentration range of flupentixol may still be considered as valid.Only few studies considered the existence of two geometric isomers of flupentixol differing by their properties. In 1985, a lower threshold of 2 ng/ml flupentixol was reported for satisfactory antipsychotic effect (Balant-Gorgia et al. 1985). The authors did not use a stereoselective method, P. Baumann, H. Kirchherr and C. Hiemke are members o...

show abstract

Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders

Mahapatra

Quraishi²,

David³

et al. 2014

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

show abstract

Occupancy of dopamine D1, D2 and serotonin2A receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol

Cited by 51 publications

References 40 publications

Dopamine Receptor Blockade Attenuates the General Incentive Motivational Effects of Noncontingently Delivered Rewards and Reward-Paired Cues Without Affecting Their Ability to Bias Action Selection

Dopamine Receptor Blockade Attenuates the General Incentive Motivational Effects of Noncontingently Delivered Rewards and Reward-Paired Cues Without Affecting Their Ability to Bias Action Selection

Flupentixol: relevance of stereoselective therapeutic drug monitoring

Flupenthixol decanoate (depot) for schizophrenia or other similar psychotic disorders

Contact Info

Product

Resources

About