Linked Life Data

10353496

Source:http://linkedlifedata.com/resource/pubmed/id/10353496

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1999-7-15
pubmed:abstractText
The present study was designed to evaluate the oral efficacy and bioavailability of ketamine. Antinociceptive efficacy was determined with the rat formalin test and oral bioavailability by the measurement of plasma and brain concentrations of ketamine and its major metabolite, norketamine. Oral ketamine in a dose range from 30 to 180 mg/kg or saline was given prior to intraplantar formalin and the flinching behavior was measured. Oral ketamine dose-dependently reduced the flinching during phase 2, while flinching during phase 1 was reduced only with the highest dose given. Following oral ketamine at 100 mg/kg, blood and brain samples were obtained and plasma and brain ketamine and norketamine levels were measured using high-performance liquid chromatography (HPLC). The average concentration ratio of norketamine/ketamine, as expressed by the area under the curve (AUC) value, was 6.4 for plasma and 2.9 for brain. These results demonstrate that a significant amount of norketamine is formed by first pass biotransformation of ketamine and is distributed to the brain. Competition binding assays for the [3H]MK-801-labeled non-competitive site of the N-methyl-D-aspartate receptor (NMDA) receptor revealed that both norketamine and ketamine displaced [3H]MK-801 at low micromolar concentrations with Ki values of 2.5 and 0.3 mM in the forebrain, and 4.2 and 1.0 mM in the spinal cord, respectively. Spinal norketamine was approximately equipotent to ketamine in producing antinociceptive effects during phase 2 of the formalin test. Thus, norketamine appears to contribute to the antinociceptive effects of oral ketamine through its NMDA receptor antagonist activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0304-3959
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
85-93
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Oral ketamine is antinociceptive in the rat formalin test: role of the metabolite, norketamine.
pubmed:affiliation
Department of Pharmacology, Cornell University Medical College, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't