A model of anticholinergic activity of atypical antipsychotic medications

Chew, Marci L.; Mulsant, Benoit H.; Pollock, Bruce G.; Lehman, Mark E.; Greenspan, Andrew; Kirshner, Margaret A.; Bies, Robert R.; Kapur, Shitij; Gharabawi, Georges M.

doi:10.1016/j.schres.2006.07.011

Cited by 124 publications

(96 citation statements)

References 55 publications

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“…Raclopride might be a false positive since its short action makes the initial DA shell peak to dominate the overall time course and result in a preferential shell pattern. Olanzapine, instead, might be a false negative, its low EPS liability being independent of a differential shell vs core pattern, but related instead to its powerful in vivo antimuscarinic properties, superimposable to those of clozapine (Bymaster et al 2003;Chew et al 2006). In fact, olanzapine has nanomolar affinity for D2 receptors and rapid blood/brain equilibration that makes it more similar to chlorpromazine than to clozapine (Jones et al 1996).…”

Section: Discussionmentioning

confidence: 99%

A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics

et al. 2014

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Apart from raclopride and olanzapine, the APs with lower extrapyramidal effects could be distinguished from typical APs on the basis of their ability to preferentially stimulate DA transmission in the NAc shell. There was no relationship between stimulation of PFCX DA and atypical APs profile. The differences between this study and voltammetry studies were not attributable to pargyline pretreatment.

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Section: Discussionmentioning

confidence: 99%

A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics

et al. 2014

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“…Thus, it is intriguing to speculate that the antimuscarinic properties of clozapine (for review see Kinon and Lieberman, 1996) mediated the effects on the performance of otherwise drug-naïve animals (see also Minzenberg et al, 2004). However, this speculation may be limited by questions about the antimuscarinic efficacy of clozapine when administered at such low dose (Chew et al, 2006). AMPH-pretreated animals were not affected by clozapine treatment.…”

Section: Discussionmentioning

confidence: 99%

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Martı́nez

Sarter

2007

Neuropsychopharmacol

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The absence of effective cognition enhancers for the treatment of patients with schizophrenia limits the validation of animal models and behavioral tests used for drug finding and characterization. However, low doses of haloperidol and clozapine were documented to produce moderately beneficial effects in patients. Therefore, this experiment was designed to determine the attentional effects of such treatments in a repeated-amphetamine (AMPH) animal model. Animals were trained in an operant-sustained attention task and underwent a 40-day pretreatment period with saline or increasing doses (1-10 mg per kg) of AMPH. After regaining baseline performance following 10 days of saline treatment, animals were treated with haloperidol (0.025 mg per kg), clozapine (2.5 mg per kg), or vehicle for 10 days. Furthermore, the effects of AMPH challenges (1.0 mg per kg) were assessed. In AMPH-pretreated animals, the administration of AMPH challenges resulted in the disruption of attentional performance. Treatment with haloperidol and clozapine attenuated the detrimental performance effects of these challenges, with clozapine exhibiting more robust attenuation. Furthermore, clozapine, but not haloperidol, impaired the performance of control animals. In contrast, the performance of AMPH-pretreated animals remained unaffected by clozapine. As this animal model detects the moderately beneficial cognitive effects of haloperidol and clozapine, it may be useful for preclinical research designed to detect and characterize treatments for the cognitive symptoms of schizophrenia.

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“…The most important are those on the cardiovascular, central, autonomic nervous system and endocrine systems. [2,[4][5][6] Knowledge of how the prevalence and severity of adverse effects vary for different antipsychotics allows the clinicians to choose the safer therapy for his patients and reduce the occurrence of these effects. [7] The present study was aimed to assess the severity of various adverse drug reactions (ADRs) associated with the utilization of various antipsychotics used in our patient suffering from different psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

Prevalence and Severity of Adverse Drug Reactions (ADRs) in patients subjected to different Anti-psychotic drugs in an Out-Patient Department of a Psychiatry Hospital in Kashmir; a prospective observational study

Ahmad¹,

Hussain²,

Farhat³

et al. 2016

IJPCS

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Background: Adverse effects are usually dose dependent and can be influenced by patient characteristics including age and gender and these confounding factors should be considered in clinical practice and in the interpretation of research data. Selection of an antipsychotic drug should be on an individual patient basis. Patients should be involved in prescribing decisions and this should involve discussion about adverse drug reactions and their severity. Objective: Current study was carried out with the aim to look into the severity with which the adverse drug reactions were associated with various antipsychotics used in our day to day practice. Materials and Methods: It was a prospective observational study conducted over a period of one year in the Outpatient Department of Institute of Mental Health and Neurosciences (IMHNS), Government Medical College Srinagar. An assessment of severity was done using modified Hartwig and Siegel scale. Results: A total of 100 ADRs of different types were observed in 77 patients out of total 177 patients included in our study, with an overall prevalence of about 43.5%. Most (83.0%) of the ADRs were mild in severity while ADRs moderate in severity were found in only 17 (17.0%) according to modified Hartwig and Siegel scale. None of the reported ADRs belonged to 'severe' or 'lethal' category. There was no statistically significant relationship between development of ADRs with age (p=0.8) or sex (p=0.6) of the patients included in the study. Conclusion: Although with the utilization of antipsychotics, the prevalence of ADRs in our study was as high 43.5%, most of them (83%) were mild in nature and only 17% of them were of moderate severity and none of our patients showed the development of any severe ADR which would lead them to discontinue the therapy.

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A model of anticholinergic activity of atypical antipsychotic medications

Cited by 124 publications

References 55 publications

A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics

A systematic microdialysis study of dopamine transmission in the accumbens shell/core and prefrontal cortex after acute antipsychotics

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Prevalence and Severity of Adverse Drug Reactions (ADRs) in patients subjected to different Anti-psychotic drugs in an Out-Patient Department of a Psychiatry Hospital in Kashmir; a prospective observational study

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