Mepiprazole, a new psychotropic drug: effects on uptake and retention of monoamines in rat brain synaptosomes.


:The influence of mepiprazole (EMD 16,923), a new pyrazol-ylalkyl-piperazine derivative, on the uptake of 3H-norepinephrine (NE), 3H-dopamine (DA), and 3H-serotonin (5-HT) into rat brain synaptosomes from cerebral cortex, corpus striatum, and hypothalamus was investigated in comparison with several psychotropic drugs, including oxypertine, d-amphetamine, imipramine, desipramine, chlorimipramine, amitriptyline, and chlorpromazine in vitro. Mepiprazole was a relatively weak inhibitor of monoamine uptake and exhibited its strongest action on the hypothalamic 5-HT uptake, being almost equipotent with desipramine (IC50 = 0.9 MUM). Furthermore, the influence of the drugs on the retention of 3H-amines previously taken up by whole rat brain synaptosomes was studied. Unlike the tricyclic antidepressants, mepiprazole as well as oxypertine and d-amphetamine markedly increased the efflux of radioactivity during a 20-min incubation at 37 degrees C at low concentrations (10(-6) to 10(-5) M), whereas at 10(-4) M all drugs greatly enhanced the efflux. The ability of mepiprazole to increase 5-HT concentration at the receptor level by a combination of neuronal uptake inhibition and release is discussed in relationship to the central actions of the drug.




Placheta P,Singer E,Kriwanek W,Hertting G




Has Abstract


1976-08-17 00:00:00












  • Human studies on the benzodiazepine receptor antagonist beta-carboline ZK 93 426: antagonism of lormetazepam's psychotropic effects.

    abstract::The effects of lormetazepam (0.03 mg/kg IV) a benzodiazepine (BZ) derivative in combination with ZK 93 426 (0.04 mg/kg IV) a beta-carboline, benzodiazepine receptor antagonist were evaluated in humans. Independently, the effects of ZK 93 426 on its own were investigated. A psychometric test battery to evaluate sedatio...


    pub_type: 临床试验,杂志文章


    authors: Duka T,Goerke D,Dorow R,Höller L,Fichte K

    更新日期:1988-01-01 00:00:00

  • Up-regulation of beta 1-adrenergic receptors in rat brain after chronic citalopram and fluoxetine treatments.

    abstract::Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of beta 1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg-1), fluoxetine ...


    pub_type: 杂志文章


    authors: Pälvimäki EP,Laakso A,Kuoppamäki M,Syvälahti E,Hietala J

    更新日期:1994-08-01 00:00:00

  • DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues.

    abstract:RATIONALE:A dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated. OBJECTIVES:The present study evaluated the relationship between carryi...


    pub_type: 临床试验,杂志文章


    authors: McClernon FJ,Hutchison KE,Rose JE,Kozink RV

    更新日期:2007-11-01 00:00:00

  • Stimulation of serotonin1B receptors induces conditioned place aversion and facilitates cocaine place conditioning in rats.

    abstract:RATIONALE:Changes in serotonin(1B) (5-HT(1B)) receptor function appear to modify the reinforcing properties of cocaine, but the direction of this effect is not completely clear. Pharmacological stimulation of 5-HT(1B) enhanced the rewarding properties of self-administered cocaine while attenuating the threshold-reducin...


    pub_type: 杂志文章


    authors: Cervo L,Rozio M,Ekalle-Soppo CB,Carnovali F,Santangelo E,Samanin R

    更新日期:2002-09-01 00:00:00

  • Effect of low-dose bromocriptine in treatment of psychosis: the dopamine autoreceptor-stimulation strategy.

    abstract::Bromocriptine (0.5-6.0 mg/day) was administered to seven unmedicated chronic schizophrenic and two schizoaffective patients. Transient slight improvement was noted in four patients and marked improvement in one other. Clinical improvement was associated with nausea and drowsiness. These doses of bromocriptine stimulat...


    pub_type: 杂志文章


    authors: Meltzer HY,Kolakowska T,Robertson A,Tricou BJ

    更新日期:1983-01-01 00:00:00

  • Effects of diphenhydramine on human eye movements.

    abstract::Peak saccadic eye movement velocity (SEV) and average smooth pursuit gain (SP) are reduced in a dose-dependent manner by diazepam and provide reliable, quantitative measures of benzodiazepine agonist effects. To evaluate the specificity of these eye movement effects for agents acting at the central GABA-benzodiazepine...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Hopfenbeck JR,Cowley DS,Radant A,Greenblatt DJ,Roy-Byrne PP

    更新日期:1995-04-01 00:00:00

  • Antalarmin, a putative CRH-RI antagonist, has transient reinforcing effects in rhesus monkeys.

    abstract:RATIONALE:During the course of our investigation of antalarmin, a corticotropin-releasing hormone (CRH) antagonist, in rhesus monkeys, we noticed that large, intravenous doses of antalarmin resulted in behavioral changes that resembled intoxication. OBJECTIVES:Antalarmin was evaluated in rhesus monkeys for its reinfor...


    pub_type: 杂志文章


    authors: Broadbear JH,Winger G,Rice KC,Woods JH

    更新日期:2002-11-01 00:00:00

  • Limitations on the use of the C57BL/6 mouse in the tail suspension test.

    abstract:RATIONALE:The C57BL/6 is one of the most widely used mouse strains in behavioral, pharmacological, and genetic research but little is known about their response on tests for antidepressant drugs. OBJECTIVES:The behavior of C57BL/6 mice, and mice from other strains, was examined in the tail suspension test (TST), a com...


    pub_type: 杂志文章


    authors: Mayorga AJ,Lucki I

    更新日期:2001-04-01 00:00:00

  • Compulsive drug seeking by rats under punishment: effects of drug taking history.

    abstract:RATIONALE:Abstinence from drug occurs in human addicts for several reasons, including the avoidance of adverse consequences. OBJECTIVES:To explore a model of drug use in the face of adverse consequences in rats through intermittent punishment of drug seeking and to investigate whether the ability to withhold seeking r...


    pub_type: 杂志文章


    authors: Pelloux Y,Everitt BJ,Dickinson A

    更新日期:2007-09-01 00:00:00

  • Yawning is elicited by D2 dopamine agonists but is blocked by the D1 antagonist, SCH 23390.

    abstract::The subtype of dopamine (DA) receptors mediating the yawning response to DA agonists was determined in rats. Yawning was elicited both by the mixed D1-D2 agonist apomorphine and by the specific D2 agonist LY 171555, but not by the selective D1 agonist SKF 38393. Both apomorphine- and LY 171555-induced yawning were ant...


    pub_type: 杂志文章


    authors: Serra G,Collu M,Gessa GL

    更新日期:1987-01-01 00:00:00

  • Effect of diazepam on the speed of mental rotation.

    abstract::The effect of diazepam on spatial visualization was studied using a double-blind crossover design. Diazepam 10 mg (or placebo) was given orally to 12 healthy young men at bedtime, followed again by 10 mg (or placebo) the next morning. One hour after the administration of the morning dose, the subjects performed a ment...


    pub_type: 临床试验,杂志文章


    authors: Taylor J,Hunt E,Coggan P

    更新日期:1987-01-01 00:00:00

  • Effects of post-trial administration of nicotine on human memory: evaluating the conditions for improving memory.

    abstract::In the studies reported here, we investigated the effects of nicotine on memory for unrelated word lists. Nicotine was delivered through cigarette smoking, and memory performance was assessed using both intentional and incidental recall tasks, and employing an additional, indirect measure of memory. We report the resu...


    pub_type: 杂志文章


    authors: Rusted J,Graupner L,Warburton D

    更新日期:1995-06-01 00:00:00

  • Behavioral performance effects of nifedipine in normotensive and renovascular hypertensive baboons.

    abstract::Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with nifedipine. Performances during a five-color simultaneous match-to-sample task were measured during three dosing schedules (0.20, 0.68, and 1.14 mg/kg/day) and vehicle. Each do...


    pub_type: 杂志文章


    authors: Turkkan JS,Hienz RD

    更新日期:1990-01-01 00:00:00

  • Relationship between variations in estradiol and progesterone levels across the menstrual cycle and human performance.

    abstract:RATIONALE:Studies about whether or not the cognitive performance of women is influenced by changes in levels of sex steroid hormones across the menstrual cycle have produced ambiguous results. OBJECTIVES:This study tested whether flight simulator performance differs significantly between the menstrual and the luteal p...


    pub_type: 杂志文章


    authors: Mumenthaler MS,O'Hara R,Taylor JL,Friedman L,Yesavage JA

    更新日期:2001-05-01 00:00:00

  • Effects of contingency management and bupropion on cigarette smoking in smokers with schizophrenia.

    abstract:RATIONALE:Individuals with schizophrenia have high smoking-related morbidity and mortality rates and need powerful and innovative smoking cessation interventions. OBJECTIVES:This proof-of-concept study investigated the feasibility and initial efficacy of combining a contingency management intervention with bupropion t...


    pub_type: 杂志文章,随机对照试验


    authors: Tidey JW,Rohsenow DJ,Kaplan GB,Swift RM,Reid N

    更新日期:2011-09-01 00:00:00

  • Interaction of apomorphine and haloperidol: effects on locomotion and other behaviour in the marmoset.

    abstract::The behavioural effects of increasing doses of apomorphine and haloperidol were observed in a group of six marmosets. Behaviour was classified quantitatively into categories: Locomotion, inactivity, checking (small head movements), social interaction and purposeful activities. Statistical analysis revealed that apomor...


    pub_type: 杂志文章


    authors: Scraggs PR,Baker HF,Ridley RM

    更新日期:1979-01-01 00:00:00

  • Tolerance to the anti-pentylenetetrazole effects of diazepam in the mouse.

    abstract::The protective effects of acute and chronic diazepam administration (4 mg/kg) against seizures induced by pentylenetetrazole (PTZ) and picrotoxin were investigated. Considering the incidence of tonic-clonic convulsions, tolerance to the protective effects of diazepam was evident by day 5 if the mice were challenged wi...


    pub_type: 杂志文章


    authors: File SE

    更新日期:1983-01-01 00:00:00

  • Effect of destruction of the 5-hydroxytryptaminergic pathways on behavioural timing and "switching" in a free-operant psychophysical procedure.

    abstract::This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for a s...


    pub_type: 杂志文章


    authors: al-Zahrani SS,Ho MY,Velazquez Martinez DN,Lopez Cabrera M,Bradshaw CM,Szabadi E

    更新日期:1996-10-01 00:00:00

  • Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes.

    abstract::The suggestions that dopamine (DA) systems are involved in "motor control" and "reward" represent the classic working hypotheses on the behavioral functions of these systems. The research generated by these hypotheses has yielded results that are far more complicated than the simplest form of either hypothesis would i...


    pub_type: 杂志文章,评审


    authors: Salamone JD

    更新日期:1992-01-01 00:00:00

  • Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients.

    abstract:RATIONALE:Perphenazine, a classical antipsychotic drug, has the potential to induce extrapyramidal side effects (EPS). Dopaminergic and serotonergic pathways are involved in the therapeutic and adverse effects of the drug. OBJECTIVES:To evaluate the impact of polymorphisms in the dopamine D(2) and D(3) and serotonin 2...


    pub_type: 临床试验,杂志文章


    authors: Gunes A,Scordo MG,Jaanson P,Dahl ML

    更新日期:2007-03-01 00:00:00

  • The relative contributions of ecstasy and cannabis to cognitive impairment.

    abstract:RATIONALE:(+/-)-3,4-methylenedioxymethamphet-amine (MDMA; 'ecstasy'), a commonly used recreational drug, has typically been found to be related to poor cognitive function in humans. However, cannabis consumption may not have been adequately controlled for in these studies. OBJECTIVE:The present study was designed to f...


    pub_type: 杂志文章


    authors: Croft RJ,Mackay AJ,Mills AT,Gruzelier JG

    更新日期:2001-01-01 00:00:00

  • Chlordiazepoxide-induced disruption of discrimination behaviour: a signal detection analysis.

    abstract::To assess the effects of chlordiazepoxide (CDP) on a stable discrimination performance, eight rats were trained on a simple brightness discrimination and injected with three dosages (0, 5, and 10 mg/kg) once performance was stable. Signal detection analysis of the results was used to differentiate sensory from motor/r...


    pub_type: 杂志文章


    authors: Francis RL,Cooper SJ

    更新日期:1979-06-21 00:00:00

  • Comparison of measured and FTC-predicted nicotine uptake in smokers.

    abstract::Cigarette smokers have a wide variety of "tar" and nicotine yields to choose from in the current market, ranging from 0.5 mg "tar" and less than 0.05 mg nicotine to 27 mg "tar" and 1.8 mg nicotine by the Federal Trade Commission (FTC) method. To understand better the relationship between FTC nicotine yields and actual...


    pub_type: 临床试验,杂志文章


    authors: Byrd GD,Robinson JH,Caldwell WS,deBethizy JD

    更新日期:1995-11-01 00:00:00

  • Selective effects of triazolam on memory.

    abstract::The effects of benzodiazepine (triazolam 0.25 and 0.50 mg) on different aspects of cognitive function were assessed. Triazolam impaired free recall and recognition of information presented after drug administration. In contrast to these impairments in explicit memory, a memory function that did not require conscious a...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Weingartner HJ,Hommer D,Lister RG,Thompson K,Wolkowitz O

    更新日期:1992-01-01 00:00:00

  • Chronic lithium attenuates dopamine D1-receptor mediated increases in acetylcholine release in rat frontal cortex.

    abstract::The effects of chronic lithium treatment on methylphenidate-, D1 dopamine receptor agonist (A-77636)-, and tactile stimulation-induced increases in frontal cortical acetylcholine release were studied in the rat using in vivo brain microdialysis. Cortical acetylcholine release in control rats was maximally stimulated b...


    pub_type: 杂志文章


    authors: Acquas E,Fibiger HC

    更新日期:1996-05-01 00:00:00

  • BIMT 17: a putative antidepressant with a fast onset of action?

    abstract::BIMT 17, the only compound reported to be a full 5-HT1A agonist and a 5-HT2A antagonist at the frontal cortex, was assessed in three animal paradigms sensitive to antidepressants in rats: olfactory bulbectomy (OB), differential-reinforcement-of-low rate 72-s (DRL 72-s) and learned helplessness (LH). In the OB rats, BI...


    pub_type: 杂志文章


    authors: Borsini F,Cesana R,Kelly J,Leonard BE,McNamara M,Richards J,Seiden L

    更新日期:1997-12-01 00:00:00

  • The acute effects of physical activity on cigarette cravings: exploration of potential moderators, mediators and physical activity attributes using individual participant data (IPD) meta-analyses.

    abstract:RATIONALE:The effects of acute bouts of physical activity (PA) on Strength of Desire (SoD) and Desire to Smoke (DtS) using individual participant data (IPD) from 19 acute randomised controlled studies were quantified. However, there is a need to identify factors influencing this relationship. OBJECTIVES:To understand ...


    pub_type: 杂志文章,meta分析,评审


    authors: Haasova M,Warren FC,Ussher M,Janse Van Rensburg K,Faulkner G,Cropley M,Byron-Daniel J,Everson-Hock ES,Oh H,Taylor AH

    更新日期:2014-04-01 00:00:00

  • Alterations in nerve terminal glutamate immunoreactivity in the nucleus accumbens and ventral tegmental area following single and repeated doses of cocaine.

    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...


    pub_type: 杂志文章


    authors: Kozell B,Meshul K

    更新日期:2003-02-01 00:00:00

  • Cognitive effects of L-deprenyl in Alzheimer's disease.

    abstract::Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. L-Dep...


    pub_type: 临床试验,杂志文章


    authors: Tariot PN,Sunderland T,Weingartner H,Murphy DL,Welkowitz JA,Thompson K,Cohen RM

    更新日期:1987-01-01 00:00:00

  • Caveolin-1 regulates medium spiny neuron structural and functional plasticity.

    abstract:RATIONALE:Caveolin-1 (CAV1) is a structural protein critical for spatial organization of neuronal signaling molecules. Whether CAV1 is required for long-lasting neuronal plasticity remains unknown. OBJECTIVE AND METHODS:We sought to examine the effects of CAV1 knockout (KO) on functional plasticity and hypothesized th...


    pub_type: 杂志文章


    authors: Eisinger KRT,Chapp AD,Swanson SP,Tam D,Lopresti NM,Larson EB,Thomas MJ,Lanier LM,Mermelstein PG

    更新日期:2020-09-01 00:00:00