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 high-Km (mean Km2 = 7691 microM) components. The low-K(m) enzyme accounted for an average of 96% of estimated intrinsic clearance, and was predicted to contribute more than 50% of net reaction velocity at phenacetin concentrations less than 2000 microM. Among index inhibitor probes, alpha-naphthoflavone was a highly potent inhibitor of the low-Km enzyme (Ki1 = 0.013 microM); furafylline also was a moderately active inhibitor (Ki1 = 4.4 microM), but its inhibiting potency was increased by preincubation with microsomes. Ketoconazole was a relatively weak inhibitor (Ki1 = 32 microM); quinidine and cimetidine showed minimal inhibiting activity. Among six selective serotonin reuptake inhibitor (SSRI) antidepressants, fluvoxamine was a potent inhibitor of 1A2 (mean Ki1 = 0.24 microM). The other SSRIs were more than tenfold less potent. Mean Ki1 values were: fluoxetine, 4.4 microM; norfluoxetine, 15.9 microM; sertraline, 8.8 microM; desmethylsertraline, 9.5 microM; paroxetine, 5.5 microM. The antidepressant nefazodone and four of its metabolites (meta-chloro-phenylpiperazine, two hydroxylated derivatives, and a triazoledione) were very weak inhibitors of P450-1A2. Venlafaxine and its O- and N-desmethyl metabolites showed minimal inhibitory activity.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
von Moltke LL,Greenblatt DJ,Duan SX,Schmider J,Kudchadker L,Fogelman SM,Harmatz JS,Shader RIdoi
10.1007/s002130050149subject
Has Abstractpub_date
1996-12-01 00:00:00pages
398-407issue
4eissn
0033-3158issn
1432-2072journal_volume
128pub_type
杂志文章abstract:RATIONALE:Although environmental enrichment renders rats more sensitive to the neurobehavioral effects of acute amphetamine, a previous study found that enriched rats self-administer less amphetamine than isolated rats at a low unit dose (0.03 mg/kg per infusion). In that study, however, acquisition of self-administrat...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1134-y
更新日期:2002-08-01 00:00:00
abstract:RATIONALE:Zidovudine (AZT) and lamivudine (3TC) are nucleoside analogues administered prenatally in clinical practice, separately or in combination, as antiretroviral drugs to prevent HIV mother-to-child transmission by inhibiting viral reverse transcriptase. In animal studies pre- and/or perinatal exposure to AZT and ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000585
更新日期:2001-02-01 00:00:00
abstract:RATIONALE:Adolescence marks a period of increased vulnerability to the development of substance use disorders. High sweet preference is a genetically mediated behavioral trait that also predicts vulnerability to substances of abuse. Previous research has shown that while adolescent rats selectively bred for high (HiS) ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2958-8
更新日期:2013-05-01 00:00:00
abstract::Central dopaminergic transmission has been implicated in memory processes. The present experiments examined the effects of several direct acting dopaminergic agents on performance of a delayed-non-match-to-sample radial arm maze task. Preadministration of apomorphine (D1-D2 agonist; 0.25, 0.5, and 1.0 mg/kg), quinpiro...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245288
更新日期:1992-01-01 00:00:00
abstract::These experiments were undertaken to determine if local injection of pilocarpine in the neostriatum of the rat produces oral motor activities that are similar to those produced by systemic administration. In the first experiment, IP administration of 2.0-8.0 mg/kg pilocarpine increased chewing movements and tongue pro...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02247136
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:In cell culture systems, agonists can promote the phosphorylation and internalization of receptors coupled to G proteins (GPCR), leading to their desensitization. However, in the CNS opioid agonists promote a profound desensitization of their analgesic effects without diminishing the presence of their recepto...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00213-005-2248-9
更新日期:2005-06-01 00:00:00
abstract:RATIONALE:We have recently shown that post-extinction exposure of rats to a sub-threshold reminder shock can reactivate extinguished context-related freezing and found that chronic treatment with fluoxetine before fear extinction prevents this phenomenon. OBJECTIVES:In the present study, we examined whether these find...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-010-2134-y
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVES:Although cocaine use has been linked to sexual HIV risk behavior for decades, the direct effects of cocaine on sexual desire and sexual decision-making are unexamined. Research suggests delay discounting (devaluation of future outcomes) and probability discounting (devaluation of uncertain outcomes) play rol...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-016-4493-5
更新日期:2017-02-01 00:00:00
abstract:RATIONALE:The characterization of self-administration (SA) under extended access conditions is necessary for the development of addiction models. OBJECTIVE:The purposes of this experiment were to investigate: (1) dose effects on the initiation of cocaine SA under extended access conditions; (2) predictable individual ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100744
更新日期:2001-08-01 00:00:00
abstract::Previous studies indicate that some aspects of endotoxin-induced sickness behavior in rats may be mediated by interleukin-1 stimulated events and can be attenuated by corticosteroids, cyclooxygenase inhibitors and the interleukin-1-receptor antagonist. In the current studies, we replicate and extend these findings in ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050353
更新日期:1997-08-01 00:00:00
abstract::2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg p...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246581
更新日期:1996-02-01 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::We have previously obtained evidence that the mesoamygdaloid dopamine projection modulates the acquisition of a conditioned response (CR) elicited by presentation of a conditioned stimulus (CS) predicting the availability of a natural (sucrose) reward. This property was found to be dependent upon D3, but not D1 or D2,...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050771
更新日期:1998-12-01 00:00:00
abstract::Different groups of rats received combined or separate administration of different doses of piracetam (P1:100, P2:200, and P4:400 mg/kg) and choline (C1:100 and C2:200 mg/kg). Compared to control treatment, C1 significantly improved performance in a delayed alternation (DA) task, while P1, P2, P4 or P1C1 had no effect...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00215480
更新日期:1987-01-01 00:00:00
abstract::When tested in adulthood, male rats that had been treated daily with 50 mg/kg hydroxyzine HCl SC at 10--29 or 23--29 days of age were significantly facilitated in performance of delayed spontaneous alternation relative to saline-injected rats. Treatment at 10--16 days of age did not produce significant facilitation in...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427646
更新日期:1980-01-01 00:00:00
abstract::Abnormal beta-adrenergic receptor (betaAR) density in the brains of suicide victims has been reported, although results of studies are inconsistent. Ethanol modifies betaAR-mediated signal transduction. Moreover abnormal betaAR function has been implicated in alcoholism. BetaAR antagonists, which were used as ligands ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130051029
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVES:Ayahuasca is a traditional South American psychoactive beverage and the central sacrament of Brazilian-based religious groups, with followers in Europe and the United States. The tea contains the psychedelic indole N,N-dimethyltryptamine (DMT) and beta-carboline alkaloids with monoamine oxidase-inhibiting pr...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-007-0963-0
更新日期:2008-02-01 00:00:00
abstract::Acute tolerance, defined as a decreasing drug effect relative to drug-plasma levels (DPL) over a period of minutes to a few hours, is pronounced following single doses of diazepam or pentobarbital. Both of these lipid-soluble drugs produce an early peak behavioral impairment and subsequent rapid recovery component tha...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427800
更新日期:1983-01-01 00:00:00
abstract::Two methods were used to assess nicotine-induced antinociception: tail withdrawal from a hot water bath and hind paw withdrawal from a hotplate. Nicotine doses which produced 75-80% maximum response were 0.75 mg/kg (free base) for tail withdrawal and 0.35 mg/kg for paw withdrawal. The peripheral blocker chlorisondamin...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246552
更新日期:1995-12-01 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:RATIONALE:Acute nicotine abstinence is associated with disruption of executive function and reward processes; however, the neurobiological basis of these effects has not been fully elucidated. METHODS:The effects of nicotine abstinence on brain function during reward-based probabilistic decision making were preliminar...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-011-2404-3
更新日期:2012-01-01 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::Single-dose pharmacokinetics of alprazolam was studied in 42 normal male volunteers (14 Caucasians, 14 American-born Asians, and 14 foreign-born Asians), after both oral and parenteral (IV) administration of a small dose (0.5 mg) of the test drug. Asians manifested significantly higher Cmax, larger AUC, slower CL and ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00216063
更新日期:1988-01-01 00:00:00
abstract:RATIONALE:Lithium is the most widely prescribed mood stabilizer, but the precise mechanism of lithium is unresolved. OBJECTIVE:We examine the effects of the administration of therapeutically relevant concentrations of lithium on the expression of brain-derived neurotrophic factor (BDNF) and its receptor, Trk B, as wel...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100871
更新日期:2001-10-01 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
abstract::An experiment was conducted to test whether centrally acting drugs could act as conditioned stimuli (CS) in a classical conditioning paradigm in which electric shock acted as the unconditioned stimulus (US) and suppression of drinking was used as an indicator of a conditioned response (CR). Thirsty rats were allowed t...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244921
更新日期:1993-01-01 00:00:00
abstract::The residual effects of three hypnotics were investigated by the method of 24-h polygraphy (EEG, EMG, and EOG). The drugs were triazolam 0.25 mg and 0.5 mg, flurazepam 15 mg and 30 mg, nitrazepam 5 mg and 10 mg, and placebo. The subjects were healthy volunteers, eight men and eight women with an average age of 34.3 ye...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00426651
更新日期:1980-01-01 00:00:00
abstract::In order to study the role of dopamine (DA) in the regulation of seizure mechanisms in man, a non-emetic dose of apomorphine, a direct stimulant of DA receptors, was administered to eight patients effected by different types of epilepsy. The EEG changes induced by apomorphine administration in comparison to those elic...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00427814
更新日期:1983-01-01 00:00:00
abstract:RATIONALE:The effect of LSD in humans has been described as occurring in two temporal phases. The behavioral effects in rats also occur in two temporal phases: an initial suppression of exploration followed by increased locomotor activity. OBJECTIVES:We decided to investigate this phenomenon from the perspective that ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-005-2183-9
更新日期:2005-07-01 00:00:00
abstract::Nefiracetam is undergoing preclinical and clinical tests as a cognition-enhancing drug in Alzheimer's disease (AD). Nicotinic cholinergic receptors are lost in AD, and nicotinic as well as muscarinic cholinergic receptors are involved in the modulation of eyeblink conditioning. Experiments were carried out using young...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050275
更新日期:1997-05-01 00:00:00