Abstract:
RATIONALE:Recent studies have suggested that the salutary actions of clozapine in schizophrenia may be due to selective activation of M(1) muscarinic receptors by clozapine and/or its major active metabolite N-desmethylclozapine. OBJECTIVE:We systematically tested this hypothesis by screening a large number of psychoactive compounds, including many atypical antipsychotic drugs, for agonist activity at cloned, human M(1), M(3) and M(5) muscarinic receptors. RESULTS:Only three of the 14 atypical antipsychotic drugs we tested were found to possess partial agonist actions at M(1) muscarinic receptors (fluperlapine, JL13, clozapine). A few additional miscellaneous compounds had a modest degree of M(1) agonist actions. Only carbachol and N-desmethylclozapine had appreciable M(3) muscarinic agonism at M(3) muscarinic receptors, although several were M(5) partial agonists including MK-212, N-desmethylclozapine and xanomeline. CONCLUSION:Although M(1) muscarinic receptor-selective partial agonists have shown promise in some preclinical antipsychotic drug models, these studies indicate that it is unlikely that the salutary actions of clozapine and similar atypical antipsychotic drugs are mediated solely by M(1) muscarinic receptor activation. It is possible, however, that the M(1) agonism of N-desmethylclozapine contributes to the uniquely beneficial actions of clozapine. Thus, these results are consistent with the notion that a balanced degree of activity at multiple biogenic amine receptors, including M(1) muscarinic agonism, is responsible for the uniquely beneficial actions of clozapine.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Davies MA,Compton-Toth BA,Hufeisen SJ,Meltzer HY,Roth BLdoi
10.1007/s00213-004-2017-1subject
Has Abstractpub_date
2005-04-01 00:00:00pages
451-60issue
4eissn
0033-3158issn
1432-2072journal_volume
178pub_type
杂志文章abstract::EEG measures have been shown to differ in human subjects who are at genetically increased risk for the development of alcoholism. In the present study, EEG was recorded in rats that were selectively bred for alcohol-preferring (P) and nonpreferring (NP) behaviors during an ethanol self-administration paradigm. In this...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244335
更新日期:1993-01-01 00:00:00
abstract::The [14C]-2-deoxyglucose method was used to map the in vivo metabolic response of glucose to savoxepine, a novel tetracyclic cyano-dibenzoxepino-azepine. Savoxepine is reported to have higher affinity for dopamine (DA) receptors in the hippocampus than in the striatum and hence should have dose-dependent, anatomically...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244849
更新日期:1994-03-01 00:00:00
abstract:RATIONALE:Beneficial effects of nicotine on cognitive processes including attention have potential therapeutic uses and have been proposed as incentives for tobacco smoking. OBJECTIVES:To establish task conditions under which the effects of nicotine on attention are obtained reliably and to characterise such effects f...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1005-6
更新日期:2002-07-01 00:00:00
abstract:RATIONALE:Observing responses bring sensory receptors into contact with environmental stimuli. In the observing-response procedure, periods in which an operant response (e.g. pressing a lever) is reinforced by drug deliveries alternate with periods in which this response is never reinforced (i.e. extinction). These alt...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-003-1390-5
更新日期:2003-05-01 00:00:00
abstract:RATIONALE:Several halogenated analogs of benztropine (BZT) have previously been characterized as potent DA uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine. In a previous study using a fixed-ratio 10 schedule, two chloro-analogs (3'-Cl-BZT and 4'-Cl-B...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000616
更新日期:2001-04-01 00:00:00
abstract:RATIONALE:Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nic...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2895-6
更新日期:2013-03-01 00:00:00
abstract:RATIONALE:Drug development is a high-risk and high failure enterprise, and studies that provide an early read on the pharmacodynamic activity of novel compounds could save time and money, increasing the efficiency of the drug development process. OBJECTIVE:Preclinical and clinical experiments were designed to examine ...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-011-2456-4
更新日期:2012-03-01 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: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
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journal_title:Psychopharmacology
pub_type: 杂志文章,评审
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更新日期:2016-05-01 00:00:00
abstract::The effects of ethanol have been studied in three strains of mice (DBA 2J, albino, and C57 BL/6J) having different populations of opiate receptors. Acute ethanol treatment induces a significant increase in striatal dopamine metabolism only in the mouse strains (C57 and albino) that are rich in enkephalinergic receptor...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427106
更新日期:1981-01-01 00:00:00
abstract::In order to validate a new animal model predictive of the profile of antiepileptic drugs, we studied the antagonism by standard antiepileptics of the EEG modifications induced by low-speed IV infusion of pentylenetetrazol (PTZ) in rats. The activity of the drugs was measured by their effects on temporal characteristic...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432718
更新日期:1985-01-01 00:00:00
abstract::Two experiments were carried out on pigeons to assess the effects of acute ethanol (ETOH) administration on a delayed pair comparison procedure. ETOH disrupted performance at the two higher doses (1.0 and 2.0 g/kg, given orally). When the initial (zero delay) performance levels of treated and untreated birds were equa...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00434411
更新日期:1980-01-01 00:00:00
abstract::This study demonstrates that the selective delta receptor antagonists ICI 174864 and naltrindole (NTI) attenuate alcohol intake in a dose-dependent manner, without altering water intake, in rats selectively bred for alcohol preference. ICI 174864 had a very limited duration of action, as evidenced by the fact that sup...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246191
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000422
更新日期:2000-06-01 00:00:00
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s00213-003-1762-x
更新日期:2004-07-01 00:00:00
abstract::The relationship between premenstrual dysphoria and alcohol acquistion and use patterns was studied in 14 women over 35 days on a clinical research ward. A 7-day drug-free baseline was followed by 21 days of alcohol availability and a post-alcohol drug-free period of 7 days. Women could earn alcohol or 50 cents for 30...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244221
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:Prepulse inhibition (PPI) and locomotor activity have been used to investigate the effects of antipsychotic and stimulant drugs and their underlying dopaminergic mechanisms. Whereas D2-like agonists consistently decreased PPI and increased locomotion in rats in previous studies, we recently reported that thes...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0511-3
更新日期:2007-04-01 00:00:00
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journal_title:Psychopharmacology
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journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
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abstract::In a placebo-controlled study, we investigated the influence of nicotine on late-day aviation performance in 15 non-smoking subjects. In a within-subjects design, subjects were tested on 2 days, each lasting 8 h and consisting of three 75-min simulator flights (late-afternoon practice, evening test, night test). Prior...
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
doi:10.1007/BF00427324
更新日期:1985-01-01 00:00:00
abstract::The modulation of spontaneous (social and individual) behaviour as a function of the age of the rat (1, 3, 6, 12, 18 and 24 months) and of scopolamine dose (0.1, 0.2, 0.3 and 0.5 mg/kg) was studied. Observations were conducted during the dark phase of the reverse light/dark schedule using a reintroduction procedure. R...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00181945
更新日期:1988-01-01 00:00:00
abstract:RATIONALE:Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic-pituitary-adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-005-2164-z
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:Marijuana intoxication appears to impair response inhibition, but it is unclear if impaired inhibition and associated brain abnormalities persist after prolonged abstinence among adolescent users. We hypothesized that brain activation during a go/no-go task would show persistent abnormalities in adolescent m...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00213-007-0823-y
更新日期:2007-10-01 00:00:00
abstract::This research compares the effects, in mice and rats, of desmethylclomipramine (DCLOM) and clomipramine (CLOM). DCLOM antagonized the hypothermia induced in mice by reserpine or apomorphine to a much greater extent than CLOM. Reserpine ptosis in mice was depressed by DCLOM only. Similarly, only DCLOM was effective in ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432256
更新日期:1982-01-01 00:00:00
abstract::Two putative predictors of placebo response were studied in three samples of psychiatric outpatients. Two groups, 73 university medical center patients and 56 college health service patients, underwent 1 week of placebo treatment. A quasi-control group of 112 patients receiving no medication waited about 1 week before...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1979-06-21 00:00:00
abstract::Two experiments examined the effect of the benzodiazepine receptor agonist, zolpidem, on palatable fluid intake in water-deprived rats. In the first experiment, pretreatment with 3.0 or 10.0 mg/kg zolpidem IP was found to increase consumption of a novel glucose drink (3% d-glucose and 0.15 sodium saccharine w/v in wat...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245521
更新日期:1993-01-01 00:00:00
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...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00439271
更新日期:1983-01-01 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