Abstract:
RATIONALE:Second-generation antipsychotics occupy dopamine D2 receptors and act as antagonists or partial agonists at these receptors. While these drugs alleviate positive symptoms in patients with schizophrenia, they are less effective for treating cognitive deficits and negative symptoms. Dopamine D3 receptors are highly expressed in areas of the brain thought to play a role in the regulation of motivation and reward-related behavior. Consequently, the dopamine D3 receptor has become a target for treating negative symptoms in combination with D2 antagonism to treat positive symptoms in patients with schizophrenia. OBJECTIVE:The purpose of this study was to determine the cariprazine receptor occupancies in brain for D2 and D3 receptors in patients with schizophrenia. METHODS:Using [(11)C]-(+)-PHNO as a radioligand, positron emission tomography (PET) scans were performed in eight patients at baseline and postdose on days 1, 4, and 15. Plasma and cerebrospinal fluid (CSF) samples were analyzed for cariprazine concentrations. RESULTS:A monotonic dose-occupancy relationship was observed for both receptor types. After 2 weeks of treatment, near complete (∼100 %) occupancies were observed for both receptors at a dose of 12 mg/day. At the lowest cariprazine dose (1 mg/day), mean D3 and D2 receptor occupancies were 76 and 45 %, respectively, suggesting selectivity for D3 over D2 receptors at low doses. An exposure-response analysis found a ∼3-fold difference in EC50 (D3 = 3.84 nM and D2 = 13.03 nM) in plasma after 2 weeks of dosing. CONCLUSION:This PET imaging study in patients with schizophrenia demonstrated that cariprazine is a D3-preferring dual D3/D2 receptor partial agonist.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Girgis RR,Slifstein M,D'Souza D,Lee Y,Periclou A,Ghahramani P,Laszlovszky I,Durgam S,Adham N,Nabulsi N,Huang Y,Carson RE,Kiss B,Kapás M,Abi-Dargham A,Rakhit Adoi
10.1007/s00213-016-4382-ysubject
Has Abstractpub_date
2016-10-01 00:00:00pages
3503-12issue
19-20eissn
0033-3158issn
1432-2072pii
10.1007/s00213-016-4382-yjournal_volume
233pub_type
杂志文章abstract::The effects of ibogaine (40 and 80 mg/kg, i.p.), an indole alkaloid proposed for the treatment of drug abuse, were determined in three different groups of rats responding under an FR10 schedule of food, cocaine or heroin reinforcement. Ibogaine (80 mg/kg, i.p.) given 60 min before the start of the session resulted in ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246099
更新日期:1995-02-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00433744
更新日期:1982-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-015-4074-z
更新日期:2016-01-01 00:00:00
abstract:RATIONALE:So-called atypical antipsychotics (AAPs) are associated with varying levels of weight gain and associated metabolic disturbances, which in patients with serious mental illness (SMI) have been linked to non-compliance and poor functional outcomes. Mechanisms underlying AAP-induced metabolic abnormalities are o...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-016-4324-8
更新日期:2016-07-01 00:00:00
abstract::The effects of dopamine agonists on self-stimulation are a matter of considerable dispute. Apomorphine has variously been reported to inhibit, have no effect on, or to facilitate lever-press self-stimulation. To investigate the possibility that these discrepancies may reflect peculiarities of the lever-press test situ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00433261
更新日期:1980-01-01 00:00:00
abstract:RATIONALE:Dopaminergic therapy improves some cognitive functions and worsens others in patients with Parkinson's disease (PD). These paradoxical effects are explained by the dopamine overdose hypothesis, which proposes that effects of dopaminergic therapy on a cognitive function is determined by the baseline dopamine l...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-016-4322-x
更新日期:2016-07-01 00:00:00
abstract::The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter-balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection an...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02244767
更新日期:1994-06-01 00:00:00
abstract::The place-preference paradigm was evaluated as a measure of morphine's positive reinforcing properties. Previous place-preference studies obtained a morphine place preference of 26%-63%. In order to examine whether differences in procedure may account for this scatter, the present experiment investigated whether there...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432040
更新日期:1984-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427448
更新日期:1984-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00433058
更新日期:1980-01-01 00:00:00
abstract:RATIONALE:Anticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined. OBJECTIVE:The potential of cannabidiol (CBD) and the fatty a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-007-0970-1
更新日期:2008-02-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-011-2503-1
更新日期:2012-04-01 00:00:00
abstract:RATIONALE:The cerebral microdialysis technique has been widely used to monitor the release of 5-hydroxytryptamine (5-HT). The extracellular concentration of 5-HT has generally been shown to change after pharmacological manipulation as expected. Extracellular levels of the metabolite, 5-hydroxyindoleaceticacid (5-HIAA) ...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-003-1736-z
更新日期:2004-03-01 00:00:00
abstract:RATIONALE AND OBJECTIVES:Previous studies have demonstrated that sensitization to repeated doses of cocaine results in prolonged changes in glutamate transmission. However, little is known about long-term changes in glutamate transmission following a single dose of cocaine. Our laboratory has previously reported that a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1296-7
更新日期:2003-02-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427524
更新日期:1979-09-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245478
更新日期:1992-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3037-5
更新日期:2013-07-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1364-z
更新日期:2003-06-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
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journal_title:Psychopharmacology
pub_type: 杂志文章
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更新日期:2018-07-01 00:00:00
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journal_title:Psychopharmacology
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更新日期:2013-01-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00176470
更新日期:1987-01-01 00:00:00
abstract:RATIONALE:Cotreatment with clorgyline shifts the development of sensitization to the D2/D3 dopamine receptor agonist quinpirole from locomotion to mouthing, an effect apparently unrelated to the monoamine oxidase inhibition property of clorgyline. This phenomenon was demonstrated in rats examined in small activity cham...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0377-4
更新日期:2006-07-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427627
更新日期:1979-11-01 00:00:00
abstract::The ability of delta 9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8 alpha, 11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E1 (PGE1) and bradykinin was tested. THC was an effective a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432273
更新日期:1979-03-28 00:00:00
abstract::The study compares the behavioral profiles induced in rats (N = 118) by the D2-dopaminergic receptor agonist quinpirole (0.03 and 0.5 mg/kg), and the D1-agonist SKF38393 (1.25-40 mg/kg), and both agonists administered together. Locomotion and snout contact frequency were reduced by the low but increased by the high do...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244813
更新日期:1992-01-01 00:00:00
abstract::We have studied striatal D2 dopamine binding in schizophrenic patients treated with the novel atypical antipsychotic drug, olanzapine. 123I iodobenzamide (IBZM) single photon emission tomography (SPET) was used to estimate striatal dopamine D2 receptor binding in vivo. Patients were recruited from a prospective, doubl...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245615
更新日期:1996-03-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245706
更新日期:1993-01-01 00:00:00
abstract:RATIONALE:Benzodiazepine agonists characteristically increase food intake in humans and non-human subjects, and the underlying mechanisms of this effect are not understood completely. OBJECTIVE:Compounds with selectivity for GABAA receptor subtypes were used to evaluate the role of GABAA receptors containing alpha1 an...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0431-2
更新日期:2006-08-01 00:00:00
abstract::The effects of 6-OHDA lesions of dopamine terminals within the amygdala were investigated on i) (+) amphetamine-induced locomotor hyperactivity and ii) the acquisition of intravenous self-administration of (+) amphetamine. The lesioned rats exhibited increased locomotor activity in response to (+) amphetamine (0.75 an...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00176851
更新日期:1988-01-01 00:00:00