| Aripiprazole in an animal model of chronic alcohol consumption and dopamine d(2) receptor occupancy in rats. | |
| | |
MedLine Citation:
|
PMID: 23421566 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
Background: Epidemiologic studies and clinical assessment of schizophrenic population have revealed a high incidence of overlap between schizophrenia and addictive disorders. Objective: The aim of the present investigation was to study the effect of aripiprazole in a preclinical animal model of chronic alcohol self-administration (CASA) and also to evaluate the influence of CASA on plasma pharmacokinetics and dopamine D(2) receptor (D(2)R) occupancy in rats. Methods: The effect of oral administration of aripiprazole (1, 3, and 10 mg/kg) on 4% alcohol intake in CASA was studied for a period of 45 min after a post-dosing interval of 60 min. Brain penetration, pharmacokinetics, and D(2)R occupancy of aripiprazole were evaluated in normal and CASA rats. Results: Aripiprazole reduced alcohol consumption in CASA rats by 13, 28, and 86% at 1, 3, and 10 mg/kg, respectively, and the effect reached statistical significance at 10 mg/kg (p < .01). At this behavioral effective dose, a decrease (75%) in total plasma apparent clearance and an increase in oral area under the concentration-time curve (3.98-fold) and bioavailability (3.50-fold) of aripiprazole was observed in CASA rats. Striatal D(2)R occupancy and brain exposure of aripiprazole were significantly higher (∼twofold) in CASA rats when compared to normal rats (p < .01). Conclusion: Chronic alcohol intake results in a significant increase in exposure of aripiprazole in plasma and brain and striatal D2R occupancy. Scientific significance: Chronic alcohol intake would increase aripiprazole exposure, thus aripiprazole dose might have to be decreased (assuming this same phenomenon occurs in humans). |
| | |
Authors:
|
Ramakrishna Nirogi; Vishwottam Kandikere; Pradeep Jayarajan; Gopinadh Bhyrapuneni; Ramanatha Saralaya; Nageswararao Muddana; Renny Abraham |
Related Documents
:
|
4051946 - Effect of adenosine and aicar on atp content and regional contractile function in reper... 18608986 - Reactivity of brain parenchymal arterioles after ischemia and reperfusion. 21689896 - Acute administration of vinpocetine, a phosphodiesterase type 1 inhibitor, ameliorates ... 19909986 - Carbon monoxide reduces pulmonary ischemia-reperfusion injury in miniature swine. 21881966 - Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with devel... 12639416 - Antioxidant effect of d-002 on gastric mucosa of rats with experimentally induced injury. |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: The American journal of drug and alcohol abuse Volume: 39 ISSN: 1097-9891 ISO Abbreviation: Am J Drug Alcohol Abuse Publication Date: 2013 Mar |
Date Detail:
|
Created Date: 2013-02-20 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7502510 Medline TA: Am J Drug Alcohol Abuse Country: England |
Other Details:
|
Languages: eng Pagination: 72-9 Citation Subset: IM |
Affiliation:
|
Department of ADME, Discovery Research, Suven Life Sciences Ltd ., Hyderabad - 500055 , India. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Bimetallic Octahedral Ruthenium-Nickel Carbido Cluster Complexes. Synthesis and Structural Character...
Next Document: Pharmacokinetic Interactions between Buprenorphine/Naloxone and Raltegravir in Subjects Receiving Ch...