A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice.

A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Research Abstract Details 

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A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Abstract Text:

Andrew B Norman,Michael R Tabet,Mantana K Norman,William R Buesing,Amadeo J Pesce,William J Ball,Andrew B Norman,Michael R Tabet,Mantana K Norman,William R Buesing,Amadeo J Pesce,William J Ball,

The predominantly human sequence, high-affinity anticocaine monoclonal antibody (mAb) 2E2 was cleared slowly from mouse blood by a first-order process with an elimination t(1/2) of 8.1 days. Infused 2E2 also produced a dramatic dose-dependent increase in plasma cocaine concentrations and a concomitant decrease in the brain cocaine concentrations produced by an i.v. injection of cocaine HCl (0.56 mg/kg). At the highest dose of 2E2 tested (3:1, mAb/drug), cocaine was not detectable in the brain. Pharmacokinetic studies showed that the normal disappearance of cocaine from plasma was described by a two-compartment pharmacokinetic model with distribution t(1/2alpha) and terminal elimination t(1/2beta) values of 1.9 and 26.1 min, respectively. In the presence of an equimolar dose of mAb 2E2, there was a 26-fold increase in the area under the plasma cocaine concentration-time curve (AUC) relative to the AUC in the absence of 2E2. Consequently, 2E2 decreased the volume of distribution of cocaine from 6.0 to 0.20 l/kg, which approximated that of 2E2 (0.28 l/kg). However, cocaine was still rapidly cleared from plasma, and its elimination was now described by a single-compartment model with an elimination t(1/2) of 17 min. Importantly, 2E2 also produced a 4.5-fold (78%) decrease in the cocaine AUC in the brain. Therefore, the effect of 2E2 on plasma and brain cocaine concentrations was predominantly caused by a change in the distribution of cocaine with negligible effects on its rate of clearance. These data support the concept of immunotherapy for drug abuse.

A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Publishing Authors By Initials

AB Norman,MR Tabet,MK Norman,WR Buesing,AJ Pesce,WJ Ball,AB Norman,MR Tabet,MK Norman,WR Buesing,AJ Pesce,WJ Ball,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research

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A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of pharmacology and experimental thera

VOLUME: 320

Page Numbers: 145-53

Journal Abbreviation: J. Pharmacol. Exp. Ther.

ISSN: 0022-3565

DAY: 5

MONTH: 10

YEAR: 2006

A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376362

A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Keywords Mesh Terms:

KEYWORDS: Tissue Distribution

MESH TERMS: pharmacology

Chemical & Substance for Abstract: A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice. Information

Substance Name: Cocaine

Registry Number: 50-36-2

Grant and Affiliation Information for A chimeric human/murine anticocaine monoclonal antibody inhibits the distribution of cocaine to the brain in mice.

AFFILIATION: Division of Neuroscience, Department of Psychiatry, University of Cincinnati, College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0559, USA. andrew.norman@uc.edu

Country: United States

AGENCY: United States NIDA

GRANT: DA12043

ACRONYM: DA

MEDLINETA: J Pharmacol Exp Ther

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