Abstract:
:The pharmacokinetics of flumazenil in the rat were determined after 2.5 mg/kg intravenous and 25 mg/kg oral administration. Following intravenous administration flumazenil was rapidly eliminated with an extremely short terminal half-life (mean +/- SE, n = 8) of 8.3 +/- 0.3 min due to a large total blood clearance of 147 +/- 7 ml/kg/min combined with a relatively small volume of distribution at steady-state of 1.33 +/- 0.07 l/kg. After oral administration flumazenil was rapidly absorbed; however, the bioavailability was low (28 +/- 4%) and variable. Flumazenil was found to be unstable in rat blood in vitro and disappeared with a half-life (mean +/- SE, n = 5) of 8.3 +/- 1 min and 31 +/- 4 min at body and room temperature, respectively. The blood samples were stabilized by addition of sodium fluoride (NaF) and cooling to 0 degrees C. The samples had to be stored at -35 degrees C when analyzed at later times. Presumably esterases in rat blood are responsible for the observed instability. A sensitive HPLC assay to measure flumazenil concentrations in small blood samples is also described.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Mandema JW,Gubbens-Stibbe JM,Danhof Mdoi
10.1007/BF02244294subject
Has Abstractpub_date
1991-01-01 00:00:00pages
384-7issue
3eissn
0033-3158issn
1432-2072journal_volume
103pub_type
杂志文章abstract::Sixteen healthy volunteers were administered midazolam followed by placebo or the benzodiazepine antagonist, flumazenil, in a double-blind, cross-over study. Flumazenil reversed midazolam-induced sedation on the subjective, psychophysiological and motor indices used. In contrast, there was little evidence of any rever...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02244252
更新日期:1991-01-01 00:00:00
abstract:RATIONALE:Therapeutic efficacy of antidepressant drugs appears to be related to their ability in producing neuroadaptive changes that restore normal brain function. Activity-regulated cytoskeletal associated protein (Arc) is an effector immediate early gene that plays a fundamental role in activity-dependent neural pla...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-008-1276-7
更新日期:2008-12-01 00:00:00
abstract:RATIONALE:Conditioned behavioral responses to discrete drug-associated cues can be modulated by the environmental context in which those cues are experienced, a process that may facilitate relapse in humans. Rodent models of drug self-administration have been adapted to reveal the capacity of contexts to trigger drug s...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-009-1657-6
更新日期:2009-12-01 00:00:00
abstract::Carbachol, muscarine, eserine and neostigmine injected into the cerebral ventricles of conscious cats evoked emotional behaviour with aggression, autonomic and motor phenomena as well as clonic-tonic convulsions. The main and the most impressive feature of the gross behavioural effects of intraventricular carbachol, m...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427131
更新日期:1979-04-11 00:00:00
abstract:RATIONALE:Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats. OBJECTIVE:This study examined the effect of cocaine self-administration on behavioral indices of sleep and ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3101-1
更新日期:2013-09-01 00:00:00
abstract::The effects of serotonergic manipulations on the escape interference engendered by exposure to inescapable shock were assessed. Consistent with the view that the behavioral interference was related to reductions of serotonin (5-HT), treatment with the 5-HT receptor blocker methysergide mimicked the effects of inescapa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00181242
更新日期:1986-01-01 00:00:00
abstract:RATIONALE:Catecholamine transmission modulates numerous cognitive and reward-related processes that can subserve more complex functions such as cost/benefit decision making. Dopamine has been shown to play an integral role in decisions involving reward uncertainty, yet there is a paucity of research investigating the c...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-015-3904-3
更新日期:2015-08-01 00:00:00
abstract::It was shown previously that behavioural effects of apomorphine (locomotor activation and stereotyped behaviour) can be conditioned when they are associated with well-defined environmental stimuli. In the present study, the hypothesis was tested that glutamatergic mechanisms play an important role either in formation ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244064
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:Schizophrenia is a complex neuropsychiatric disorder characterized, in part, by impaired dopamine signaling. TAK-063 is a selective inhibitor of phosphodiesterase 10A, a key regulator of intracellular signaling pathways that is highly expressed in the striatum. OBJECTIVE:Safety, tolerability, and pharmacokin...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-016-4412-9
更新日期:2016-10-01 00:00:00
abstract::Monoamine oxidase inhibitors (MAOIs) are widely accepted as effective antidepressants. Unfortunately their use has been limited by their capacity to potentiate dietary tyramine (the so called "cheese effect") and their interaction with other drugs. The latter poses a particular problem for patients undergoing anaesthe...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF02246234
更新日期:1992-01-01 00:00:00
abstract:OBJECTIVE:To compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. METHODS:Eighty hospitalized patients with schizophrenia (DSM-IV) were randomly assigned to treatment with paliperidone ER or olanzapine for a period of 12 weeks. At baseline and ever...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-013-3073-1
更新日期:2013-11-01 00:00:00
abstract::Chlordiazepoxide (5 and 10 mg/kg) and diazepam (2.5 mg/kg) reduced the latency to eat and enhanced feeding response to familiar food in a food-preference test. The increased feeding response resulted from an increased frequency of individual eating episodes (bouts) without significant change in the episode duration. E...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426525
更新日期:1980-01-01 00:00:00
abstract:RATIONALE AND OBJECTIVE:Estradiol decline has been associated with depression and anxiety in post-menopausal women. Agomelatine (Ago) is an agonist of the melatonergic MT1/MT2 receptors and an antagonist of the serotonergic 5-HT2c receptors. The present study aimed to evaluate the effects of combining Ago with 17β-estr...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05580-2
更新日期:2020-09-01 00:00:00
abstract:RATIONALE:Schizophrenia is characterized by a large variety of cognitive symptoms, among which information processing deficits have been extensively studied. So far, these aspects have been found to be remarkably stable and effective treatment is still lacking. Traditionally, information processing is subdivided into p...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-003-1684-7
更新日期:2004-06-01 00:00:00
abstract::Chronic administration of the benzodiazepine (BZ) receptor agonist chlordiazepoxide (CDP) produced tolerance to its motor-impairing effects but little or no tolerance to its hypothermic effects or to its amnesic effects in the radial arm maze. Male Sprague-Dawley rats were pretreated for 14 days with CDP (25 mg/kg, b....
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244749
更新日期:1994-06-01 00:00:00
abstract::The purpose of this review was to establish in vivo apparent pA2 and pKB values for antagonism of the discriminative stimulus effects of benzodiazepine ligands, and to compare these values to those obtained from other behavioral procedures. Articles were chosen from the Medline data base from January 1976 to August 19...
journal_title:Psychopharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s002130050103
更新日期:1996-11-01 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
abstract::The present study compared cocaine-induced hyperlocomotion and cocaine i.v. self-administration in DBA/2J and C57BL/6J mice. In the locomotor activity experiment, these strains were tested for hyperlocomotion after i.p. cocaine injection (0-60.0 mg/kg), using a Digiscan Animal Activity Monitoring System. In the cocain...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050648
更新日期:1998-07-01 00:00:00
abstract::Previous work in this and another laboratory has shown that nicotine tablets improve the performance of a rapid information processing task and reduce the Stroop effect, whereas scopolamine has the opposite effects. The purpose of this study was to extend these previous findings by determining whether, when administer...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00432014
更新日期:1984-01-01 00:00:00
abstract::Pigeons were trained to peck each of two response keys. Periods during which pecks on one key (the food key) produced access to grain according to a random-ratio 80 schedule alternated irregularly with periods during which food-key responses had no scheduled consequences (extinction). Both keys remained amber unless a...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00422418
更新日期:1981-01-01 00:00:00
abstract:RATIONALE:The integrity of cortical cholinergic transmission is vital to attentional processing. A growing literature suggests that alterations in attentional processing accompany addictive drug use. This study examined the effects of acute and repeated administration of nicotine on cortical acetylcholine release. OBJ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1260-6
更新日期:2003-02-01 00:00:00
abstract:RATIONALE:Carrageenan-induced hyperalgesia is a widely used pain model in rodents. However, characteristics of carrageenan-induced hyperalgesia and effects of analgesic drugs under these conditions are unknown in nonhuman primates. OBJECTIVE:The aims of this study were to develop carrageenan-induced hyperalgesia in rh...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3341-0
更新日期:2014-04-01 00:00:00
abstract::The present report investigated several parametric and pharmacological aspects of the enhanced self-grooming behavior of rats following systemic administration of the selective D1 dopamine (DA) receptor agonist SKF 38393. The amount of time that rats spent grooming themselves was measured continuously for 30 min follo...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245478
更新日期:1992-01-01 00:00:00
abstract::Nicotine (6 mg/kg/day) was administered subcutaneously via Alzet osmotic pumps to rats for 28 days. Nociception was measured by the hot-plate and tail-flick methods. A significant antinociceptive effect was demonstrated during the first week of the treatment; after that tolerance developed, lasting for the remaining p...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245428
更新日期:1992-01-01 00:00:00
abstract::Nine depressed patients were treated with alaproclate, a selective 5-HT uptake inhibitor, for 3 weeks in a dose of 400 mg daily. The pupillary responses to tyramine, phenylephrine, and pilocarpine eye drops were measured on consecutive days before, after 1 week and after 3 weeks of treatment. The tyramine-induced mydr...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427324
更新日期:1985-01-01 00:00:00
abstract::Animal and human studies have demonstrated that, depending upon the sequence of alcohol presentation, long-term memory of events can either be enhanced or diminished. In the present study a similar phenomenon is demonstrated in the neuronal excitability of slices of hippocampus from guinea pig brains. Alcohol given af...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426380
更新日期:1984-01-01 00:00:00
abstract:RATIONALE:Central cannabinoid systems have been implicated in appetite regulation through the hyperphagic effects of exogenous and endogenous cannabinoids. These effects may involve activation of reward systems and be mediated in part by opioidergic processes. OBJECTIVE:Cannabinoid-opioid interactions in feeding were ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000596
更新日期:2001-01-01 00:00:00
abstract::We examined the effects on sucrose consumption of a dopamine (DA) D2/D3 antagonist (raclopride, 0-0.3 mg/kg), a serotonin 5-HT2/2c antagonist (ritanserin, 0-0.4 mg/kg), and raclopride (0.15 mg/kg) combined with ritanserin (0-0.4 mg/kg). Three different concentrations of sucrose solution (0.7%, 7.0% and 34%) were teste...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246286
更新日期:1996-01-01 00:00:00
abstract::The neurochemical specificity of physiological, biochemical, and psychological responses to dextroamphetamine was tested by pretreating volunteers with haloperidol (0.014 mg/kg IM), propranolol (0.1 mg/kg IV), thymoxamine (0.1 mg/kg IV), or placebo prior to 0.3 mg/kg IV amphetamine. Healthy volunteers (N = 12) partici...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00427446
更新日期:1984-01-01 00:00:00
abstract:RATIONALE:Alzheimer's disease (AD) is characterized by memory loss and synaptic damage. Previous studies suggested that xanthoceraside decreases glutamate-induced PC12 cell death, ameliorates memory deficits, and increases the number of dendritic spines in AD mice. These results indicated that xanthoceraside might have...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4775-6
更新日期:2018-01-01 00:00:00