Abstract:
RATIONALE:Several antipsychotic drugs are metabolised by the polymorphic cytochrome P(450) CYP2D6. The impact of the polymorphism on the plasma levels and the occurrence of side effects have not been clearly established. OBJECTIVE:To investigate the impact of the CYP2D6 polymorphism on the steady-state plasma concentrations of zuclopenthixol and the occurrence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) during treatment with zuclopenthixol-decanoate. METHODS:Fifty-two clinically stable schizophrenic outpatients on monotherapy with zuclopenthixol-decanoate (100-400 mg/4 weeks) were genotyped for the CYP2D6 variants CYP2D6*3 and CYP2D6*4. Steady-state plasma levels of zuclopenthixol were analysed using high-performance liquid chromatography. Assessments of EPS, TD and psychopathology were performed twice with an 8-week interval using the extrapyramidal symptoms rating scale, the abnormal involuntary movement scale and the brief psychiatric rating scale. RESULTS:Thirty-five patients were homozygous extensive metabolisers (EMs), 13 were heterozygous EMs and 4 were poor metabolisers (PMs). While there were no significant genotype-related differences in the doses of zuclopenthixol decanoate, PMs as well as heterozygous EMs had significantly higher steady-state plasma levels of zuclopenthixol than homozygous EMs (median 9.5 nmol/l; 8.2 nmol/l and 5.9 nmol/l, respectively, P<0.05). The median dose-corrected plasma concentrations were 0.029, 0.038 and 0.048 nmol.l(-1).mg(-1) in homozygous EMs, heterozygous EMs and PMs, respectively, with statistically significant differences between homozygous EMs and heterozygous EMs ( P=0.014) and homozygous EMs and PMs ( P=0.03). Patients with neurological side effects were significantly older than patients without ( P=0.02 in case of parkinsonism and P=0.04 in case of TD). Mutant CYP2D6*3 and *4 alleles tended to occur more frequently in patients with neurological side effects. An odds ratio (OR) of 2.3 (95% confidence interval 0.7-6.9) for development of parkinsonism and an OR of 1.7 (95% confidence interval 0.5-4.9) for TD was calculated in an individual with at least one mutated allele. However, the ORs were not statistically significant. CONCLUSIONS:The higher zuclopenthixol steady-state plasma concentrations in heterozygous EM and PM schizophrenic patients receiving monotherapy with zuclopenthixol-decanoate than in homozygous EMs indicates a significant role of CYP2D6 in the systemic elimination of zuclopenthixol. The tendencies for patients carrying at least one mutated CYP2D6 gene to have an increased risk of parkinsonism and TD are in accordance with previous studies. Age was a significant risk factor for neurological side effects.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Jaanson P,Marandi T,Kiivet RA,Vasar V,Vään S,Svensson JO,Dahl MLdoi
10.1007/s00213-002-1059-5subject
Has Abstractpub_date
2002-06-01 00:00:00pages
67-73issue
1eissn
0033-3158issn
1432-2072journal_volume
162pub_type
杂志文章abstract:RATIONALE:Executive function impairment, as classically assessed using the Wisconsin Card Sort Test or intradimensional/extradimensional tests, is a key feature of schizophrenia but remains inadequately treated by existing therapies. Recently, however, erythropoietin has been shown to improve attentional set-shifting p...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1990-9
更新日期:2010-12-01 00:00:00
abstract::The present study was conducted to determine whether methadone maintenance alters the pharmacodynamic effects of single doses of cocaine. Twenty-two current users of IV cocaine who were not seeking treatment for their illicit cocaine use participated while living on a research unit. Eleven were maintained on methadone...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02246276
更新日期:1996-01-01 00:00:00
abstract::The effects of a new alpha-2 adrenoceptor antagonist on erectile function was assessed in 12 normal volunteers (mean age 28.7, range 20-42), using a double blind, placebo controlled design with two doses of drug and three testing sessions. The drug was administered by intravenous infusion and erectile responses to ero...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02245569
更新日期:1994-08-01 00:00:00
abstract::Biotransformation of phenacetin via O-deethylation to acetaminophen, an index reaction reflecting activity of Cytochrome P450-1A2, was studied in microsomal preparations from a series of human livers. Acetaminophen formation was consistent with a double Michaelis-Menten system, with low-Km (mean Km1 = 68 microM) and h...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050149
更新日期:1996-12-01 00:00:00
abstract:RATIONALE:Developmental lead exposure may alter responsiveness to cocaine well into adulthood, and ultimately influence drug-use patterns. OBJECTIVES:The present study examined the effect of perinatal lead exposure on the discriminative stimulus properties of cocaine. METHODS:Female rats were treated with 0, 8, or 16...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100877
更新日期:2001-11-01 00:00:00
abstract::Ro 15-4513, a partial inverse agonist at the benzodiazepine (BZ) receptor site was labelled with 11C and used for in vitro autoradiography on human post mortem brain sections and for positron emission tomography (PET) on Cynomolgus monkeys. The total radiochemical yield of [11C]Ro 15-4513 was 30-40% with an overall sy...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245279
更新日期:1992-01-01 00:00:00
abstract::The behavioral effects of repeated methylphenidate (MPH) treatment were assessed in the adult rat. Protein kinase A (PKA) and adenylyl cyclase (basal and DA-stimulated) activity in the dorsal striatum (i.e., caudate-putamen) were measured to determine whether MPH-induced alterations in these enzymes correlate with the...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050536
更新日期:1998-03-01 00:00:00
abstract::This study examined and compared withdrawal signs and symptoms from cessation of 0, 2 and 4 mg nicotine gum. In addition, a comparison was made between nicotine gum versus cigarette withdrawal symptoms. Smokers first underwent cigarette deprivation for 4 days and then were randomly assigned to 0 (N = 16), 2 (N = 25), ...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02245656
更新日期:1991-01-01 00:00:00
abstract::Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia, and has a low propensity to cause extrapyramidal symptoms. The compound has a relatively short plasma elimination half-life (approximately 7 h). However, since dop...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s002130050603
更新日期:1998-05-01 00:00:00
abstract::Chronic exposure to very mild unpredictable stress has previously been found to depress the consumption of, and preference for, highly palatable sweet solutions. The present study used the place conditioning procedure to investigate whether these effects result from a decreased sensitivity to reward. Rats were subject...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244188
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:Recent data suggest that 5-HT7 receptors (5-HT7R) are involved in memory processes and, particularly, those related to novelty-induced arousal, even though this remains so far speculative and controversial. In order to assess the role of 5-HT7R in episodic-like memory, mice were administered 5-carboxamidotryp...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3247-x
更新日期:2014-01-01 00:00:00
abstract::Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22 h. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the sec...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00439545
更新日期:1989-01-01 00:00:00
abstract:RATIONALE:Major depression is a chronic disabling disorder, often preceded by stress. Despite emerging clinical interest in mechanisms perpetuating episodes of depression and/or establishing increased vulnerability for relapse, little attention has been paid to address these aspects in experimental models. Here, we stu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-1835-6
更新日期:2010-06-01 00:00:00
abstract::This was a 4-week, three-center, double-blind, randomized, parallel, placebo-controlled evaluation of the efficacy and safety of bupropion in hospitalized depressed patients. Results from 27 placebo and 48 bupropion-treated patients were analyzed for efficacy and safety. Assessments of efficacy and safety were made at...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00433415
更新日期:1983-01-01 00:00:00
abstract::The effect of long-term lithium carbonate treatment on parameters of immediate, short-, and long-term memory was examined in a group of bipolar affectively ill patients. The lithium treatment group recalled significantly fewer words across trials on a verbal learning task than a group of bipolar affectively ill patien...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426919
更新日期:1979-05-08 00:00:00
abstract:RATIONALE:State-dependent changes in physiological arousal may influence impulsive behaviours. OBJECTIVES:To examine the relationship between arousal and impulsivity, we assessed the effects of yohimbine (an α2-adrenergic receptor antagonist, which increases physiological arousal via noradrenaline release) on performa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-018-5160-9
更新日期:2019-06-01 00:00:00
abstract:RATIONALE:Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an i...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3689-9
更新日期:2015-02-01 00:00:00
abstract:RATIONALE:Cocaine and opioids are often co-abused. As yet, however, there is no clear evidence that the drugs interact to make the mixture a more effective reinforcer. OBJECTIVE:The present study examined the relative reinforcing potency and maximum effectiveness of the cocaine-opioid combination in monkeys given a ch...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-2131-1
更新日期:2011-05-01 00:00:00
abstract:RATIONALE:The startle reflex to a sudden intense acoustic pulse stimulus is attenuated if the pulse is shortly preceded by a weak prepulse stimulus. This represents a form of sensory gating, known as prepulse inhibition (PPI), observable across species. PPI is modulated by dopamine and readily disrupted by acute amphet...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2819-5
更新日期:2013-01-01 00:00:00
abstract::The effects of the enantiomers of 3-PPP on the maintenance of conditioned avoidance responding (CAR) were studied. The weak classical dopamine (DA) agonist (+)-3-PPP failed to interfere with CAR at any dose tested (0.8-13.6 mg/kg). Low doses of the drug produced sedation, while high doses produced behavioural stimulat...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00439266
更新日期:1983-01-01 00:00:00
abstract::Development of tolerance to neuroleptic compounds tested in the conditional avoidance model was investigated. Since tolerance may manifest itself by a diminished potency and/or a shortened duration of effect, the complete time course of effect was registered in these experiments. Rats were pretreated approximately 2 w...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426314
更新日期:1976-12-21 00:00:00
abstract:RATIONALE:Although the subjective effects of caffeine abstinence, acute and chronic administration, and tolerance are well described, the corresponding neurophysiological effects are not. OBJECTIVES:Caffeine withdrawal, acute caffeine effects, caffeine tolerance, and net beneficial effects of chronic caffeine administ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-009-1489-4
更新日期:2009-07-01 00:00:00
abstract:RATIONALE:Nicotine displays rewarding and aversive effects, and while dopamine has been linked with nicotine's reward, the neurotransmitter(s) involved with aversion remains speculative. The kappa-dynorphinergic system has been associated with negative motivational and affective states, and whether dynorphin (Dyn) cont...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-008-1315-4
更新日期:2009-01-01 00:00:00
abstract:RATIONALE:Dopamine innervation of the nucleus accumbens is thought to have a major role in the biological processes underlying cocaine self-administration. Recent data suggest that dopamine innervation of the ventral pallidum (VP) may also play an important role. OBJECTIVES:This experiment was initiated to assess extr...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000456
更新日期:2000-07-01 00:00:00
abstract::Rats were made hyperphagic by 6-hydroxydopamine (6-OHDA) injected bilaterally into the ventral midbrain; then they were restricted to a 6 h/day feeding schedule and tested for appetite suppression with amphetamine and fenfluramine in randomized order. Amphetamine anorexia was diminished while fenfluramine anorexia was...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426393
更新日期:1984-01-01 00:00:00
abstract::There is an increasing prevalence of smokeless tobacco use. However, very little descriptive information is available on the pattern of use. This study examines topographical features of smokeless tobacco use in a male college-age population (N = 56). Subjects were required to use smokeless tobacco ad lib. for a perio...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00216076
更新日期:1988-01-01 00:00:00
abstract::The purpose of this study was to determine whether repeated treatment (15 days) with d-amphetamine (AMP) or fenfluramine (FEN), administered after a daily 3 h feeding session (e.g. post-session), would result in tolerance or cross-tolerance to the decrement in food consumption induced by treatment with either drug bef...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00435853
更新日期:1981-01-01 00:00:00
abstract:RATIONALE:Delta-opioid agonists produce a number of behavioral effects, including convulsions, antinociception, locomotor stimulation, and antidepressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-005-0138-9
更新日期:2005-11-01 00:00:00
abstract:RATIONALE:Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000506
更新日期:2000-10-01 00:00:00
abstract::A novel form of experimentally-induced conflict behavior based on the conditioned suppression of drinking (CSD) is described and compared with two conventional animal models of human anxiety--a modified Geller-Seifter and an Estes-Skinner (Conditioned Emotional Response) procedure. The CSD procedure offered significan...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427112
更新日期:1981-01-01 00:00:00