Linked Life Data

18772033

Source:http://linkedlifedata.com/resource/pubmed/id/18772033

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2008-9-5
pubmed:abstractText
Atypical antipsychotic drugs related to clozapine, improve psychosis, cognition and negative symptoms, while producing minimal extrapyramidal side effects, in patients with schizophrenia. This appears to be mediated mainly through the combined effect of relatively more potent blockade of 5-HT(2A) receptors, located on cortical and hippocampal glutamatergic and GABAergic neurons, as well as cell bodies of the mesolimbic and mesocortical dopamine (DA) neurons, and weaker blockade of D(2) receptors in the ventral and dorsal striatum and pyramidal neurons in cortical areas, as well as the cell bodies of DA neurons. This combination of effects is important to their ability to enhance cortical and hippocampal DA efflux, which, while producing less increase of DA efflux in the striatum. Selective inverse agonists of 5-HT(2A) receptors alone, or in combination with subthreshold doses of atypical antipsychotic drugs have shown effects similar to those of atypicals in both animal models and clinical trials in patients with schizophrenia. Atypical antipsychotic drugs and 5-HT(2A) receptor antagonists/inverse agonists have been found to prevent or reverse acute and chronic effects of the N-methyl-D-aspartate non-competitive antagonist, phencyclidine (PCP), including cognitive impairment, in part through enhancing the turnover of DA in cortex. PET, postmortem and genetic studies, as well as clinical studies with 5-HT(2A) hallucinogens, strongly support the importance of 5-HT(2A) receptor blockade in the action of atypical antipsychotic drugs. Their 5-HT(1A) receptor partial agonism, produced directly or indirectly, also contributes to enhancement of efflux of DA in cortical regions. Other serotonergic actions, e.g. 5-HT(2C), 5-HT(6) and possibly 5-HT(7) antagonism, may also contribute to their efficacy or, in the case of 5-HT(2C) antagonism, side effects such as weight gain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1875-7855
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-97
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
In vivo actions of atypical antipsychotic drug on serotonergic and dopaminergic systems.
pubmed:affiliation
Department of Psychiatry, Vanderbilt University School of Medicine, Psychiatric Hospital at Vanderbilt, Nashville, TN 37212, USA. herbert.meltzer@vanderbilt.edu
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't