Linked Life Data

12065741

Source:http://linkedlifedata.com/resource/pubmed/id/12065741

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-6-14
pubmed:abstractText
Aripiprazole is the first next-generation atypical antipsychotic with a mechanism of action that differs from currently marketed typical and atypical antipsychotics. Aripiprazole displays properties of an agonist and antagonist in animal models of dopaminergic hypoactivity and hyperactivity, respectively. This study examined the interactions of aripiprazole with a single population of human D2 receptors to clarify further its pharmacologic properties. In membranes prepared from Chinese hamster ovary cells that express recombinant D2L receptors, aripiprazole bound with high affinity to both the G protein-coupled and uncoupled states of receptors. Aripiprazole potently activated D2 receptor-mediated inhibition of cAMP accumulation. Partial receptor inactivation using the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) significantly reduced the maximum effect of aripiprazole on inhibition of cAMP accumulation. This effect was seen with concentrations of EEDQ that did not alter the maximal inhibitory effect of dopamine. Consistent with the expected effects of a partial agonist, increasing concentrations of aripiprazole blocked the action of dopamine with maximal blockade equal to the agonist effect of aripiprazole alone. The efficacy of aripiprazole relative to that of dopamine varied from 25% in cells that lacked spare receptors for dopamine to 90% in cells with receptor reserve. These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer. The receptor activity profile may underlie the unique activity of aripiprazole in animals and its antipsychotic activity in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine, http://linkedlifedata.com/resource/pubmed/chemical/Antipsychotic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Forskolin, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Piperazines, http://linkedlifedata.com/resource/pubmed/chemical/Quinolones, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D2, http://linkedlifedata.com/resource/pubmed/chemical/Spiperone, http://linkedlifedata.com/resource/pubmed/chemical/aripiprazole
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
302
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
381-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.
pubmed:affiliation
Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't