ArticleDrug metabolism and disposition: the biological fate of chemicals2014
A recombinant humanized anti-cocaine monoclonal antibody inhibits the distribution of cocaine to the brain in rats.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Synthesis and characterization of a functional benzoylecgonine - bovine serum albumin conjugate for quantification of a humanized monoclonal anti-cocaine antibody.Biochemistry and biophysics reports · 2025Article
- Selective real-time disulfide reduction with simultaneous fluorescent labeling of a humanized anti-cocaine mAb.Biochemistry and biophysics reports · 2025Article
- Decreased solubility and increased adsorptivity of a biotinylated humanized anti-cocaine mAb.Analytical biochemistry · 2025Article
- Novel partial reduction of the humanized anti-cocaine mAb h2E2 for selective cysteine labeling.Biochemical and biophysical research communications · 2024Article
- Toxicokinetics of a humanized anti-cocaine monoclonal antibody in male and female rats and lack of cross-reactivity.Human vaccines & immunotherapeutics · 2023Review
- SCH23390 and a humanized anti-cocaine mAb decrease the latency to cocaine-induced reinstatement of lever pressing behavior in rats that self-administer cocaine.Scientific reports · 2023Article
- Characterization and optimization of fluorescein isothiocyanate labeling of humanized h2E2 anti-cocaine mAb.Biochemistry and biophysics reports · 2023Article
- Reformulation and Thermal Stability of a Therapeutic Anti-Cocaine mAb.Journal of pharmaceutical sciences · 2023Article
- A humanized anti-cocaine mAb antagonizes the cardiovascular effects of cocaine in rats.Pharmacology research & perspectives · 2023Article
- Isothermal titration calorimetry determination of thermodynamics of binding of cocaine and its metabolites to humanized h2E2 anti-cocaine mAb.Biochemistry and biophysics reports · 2022Article
- Effects of a recombinant humanized anti-cocaine monoclonal antibody on the metabolism and distribution of cocaine in vitro and in mice.Pharmacology research & perspectives · 2022Review
- Tyrosine nitration of a humanized anti-cocaine mAb differentially affects ligand binding of cocaine and its metabolites.Biochemistry and biophysics reports · 2022Article
- Cocaine binding to the Fab fragment of a humanized anti-cocaine mAb quantitated by dye absorption and fluorescence spectroscopy.Journal of immunological methods · 2021Article
- Ligand binding to a humanized anti-cocaine mAb measured by dye absorption spectroscopy.Biochemical and biophysical research communications · 2021Article
- Multi-domain unfolding of the Fab fragment of a humanized anti-cocaine mAb characterized by non-reducing SDS-PAGE.Biochemical and biophysical research communications · 2020Article
- Ligand binding to a humanized anti-cocaine mAb detected by non-reducing SDS-PAGE.Biochemistry and biophysics reports · 2020Article
- A novel differential scanning fluorimetry analysis of a humanized anti-cocaine mAb and its ligand binding characteristics.Journal of immunological methods · 2020Article
- Structural analysis of free and liganded forms of the Fab fragment of a high-affinity anti-cocaine antibody, h2E2.Acta crystallographica. Section F, Structural biology communications · 2019Article
- A Recombinant Humanized Anticocaine Monoclonal Antibody Alters the Urinary Clearance of Cocaine and Its Metabolites in Rats.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Domain unfolding of monoclonal antibody fragments revealed by non-reducing SDS-PAGE.Biochemistry and biophysics reports · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd) and specificity for cocaine over its inactive metabolites benzoylecgonine (BE) and ecgonine methyl ester. In rats, pharmacokinetic studies of h2E2 (120 mg/kg i.v.) showed a long terminal elimination half-life of 9.0 days and a low volume of distribution at steady state (Vdss) of 0.3 l/kg. Pretreatment with h2E2 produced a dramatic 8.8-fold increase in the area under the plasma cocaine concentration-time curve (AUC) and in brain a concomitant decrease of 68% of cocaine's AUC following an i.v. injection of an equimolar cocaine dose. Sequestration of cocaine in plasma by h2E2, shown via reduction of cocaine's Vdss, indicates potential clinical efficacy. Although the binding of cocaine to h2E2 in plasma should inhibit distribution and metabolism, the elimination of cocaine remained multicompartmental and was still rapidly eliminated from plasma despite the presence of h2E2. BE was the major cocaine metabolite, and brain BE concentrations were sixfold higher than in plasma, indicating that cocaine is normally metabolized in the brain. In the presence of h2E2, brain BE concentrations were decreased and plasma BE was increased, consistent with the observed h2E2-induced changes in cocaine disposition. The inhibition of cocaine distribution to the brain confirms the humanized mAb, h2E2, as a lead candidate for development as an immunotherapy for cocaine abuse.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.