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Development of an Effective Monoclonal Antibody against Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine and Morphine over Heroin
[Image: see text] The opioid epidemic is a global public health crisis that has failed to abate with current pharmaceutical treatments. Moreover, these FDA-approved drugs possess numerous problems such as adverse side effects, short half-lives, abuse potential, and recidivism after discontinued use....
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615117/ https://www.ncbi.nlm.nih.gov/pubmed/36313156 http://dx.doi.org/10.1021/acscentsci.2c00977 |
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author | Lee, Jinny Claire Eubanks, Lisa M. Zhou, Bin Janda, Kim D. |
author_facet | Lee, Jinny Claire Eubanks, Lisa M. Zhou, Bin Janda, Kim D. |
author_sort | Lee, Jinny Claire |
collection | PubMed |
description | [Image: see text] The opioid epidemic is a global public health crisis that has failed to abate with current pharmaceutical treatments. Moreover, these FDA-approved drugs possess numerous problems such as adverse side effects, short half-lives, abuse potential, and recidivism after discontinued use. An alternative treatment model for opioid use disorders is immunopharmacotherapy, where antibodies are produced to inhibit illicit substances by sequestering the drug in the periphery. Immunopharmacotherapeutics against heroin have engaged both active and passive vaccines targeting heroin’s metabolites, 6-monoacetylmorphine (6-AM) and morphine, since decades of research have stated that heroin’s psychoactive and lethal effects are mainly attributed to these compounds. However, concerted efforts to develop effective immunopharmacotherapies against heroin abuse have faced little clinical advancement, suggesting a need for reassessing drug target selection. To address this issue, four unique monoclonal antibodies were procured with distinct affinity to either heroin, 6-AM, or morphine. Examination of these antibodies through in vitro and in vivo tests revealed monoclonal antibody 11D12 as the optimal therapeutic and provided crucial insights into the key chemical species to target for blunting heroin’s psychoactive and lethal effects. These findings offer clarification into the problematic attempts of therapeutics targeting heroin’s metabolites and provide a path forward for future heroin immunopharmacotherapy development. |
format | Online Article Text |
id | pubmed-9615117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-96151172022-10-29 Development of an Effective Monoclonal Antibody against Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine and Morphine over Heroin Lee, Jinny Claire Eubanks, Lisa M. Zhou, Bin Janda, Kim D. ACS Cent Sci [Image: see text] The opioid epidemic is a global public health crisis that has failed to abate with current pharmaceutical treatments. Moreover, these FDA-approved drugs possess numerous problems such as adverse side effects, short half-lives, abuse potential, and recidivism after discontinued use. An alternative treatment model for opioid use disorders is immunopharmacotherapy, where antibodies are produced to inhibit illicit substances by sequestering the drug in the periphery. Immunopharmacotherapeutics against heroin have engaged both active and passive vaccines targeting heroin’s metabolites, 6-monoacetylmorphine (6-AM) and morphine, since decades of research have stated that heroin’s psychoactive and lethal effects are mainly attributed to these compounds. However, concerted efforts to develop effective immunopharmacotherapies against heroin abuse have faced little clinical advancement, suggesting a need for reassessing drug target selection. To address this issue, four unique monoclonal antibodies were procured with distinct affinity to either heroin, 6-AM, or morphine. Examination of these antibodies through in vitro and in vivo tests revealed monoclonal antibody 11D12 as the optimal therapeutic and provided crucial insights into the key chemical species to target for blunting heroin’s psychoactive and lethal effects. These findings offer clarification into the problematic attempts of therapeutics targeting heroin’s metabolites and provide a path forward for future heroin immunopharmacotherapy development. American Chemical Society 2022-10-06 2022-10-26 /pmc/articles/PMC9615117/ /pubmed/36313156 http://dx.doi.org/10.1021/acscentsci.2c00977 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Lee, Jinny Claire Eubanks, Lisa M. Zhou, Bin Janda, Kim D. Development of an Effective Monoclonal Antibody against Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine and Morphine over Heroin |
title | Development of
an Effective Monoclonal Antibody against
Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine
and Morphine over Heroin |
title_full | Development of
an Effective Monoclonal Antibody against
Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine
and Morphine over Heroin |
title_fullStr | Development of
an Effective Monoclonal Antibody against
Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine
and Morphine over Heroin |
title_full_unstemmed | Development of
an Effective Monoclonal Antibody against
Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine
and Morphine over Heroin |
title_short | Development of
an Effective Monoclonal Antibody against
Heroin and Its Metabolites Reveals Therapies Have Mistargeted 6-Monoacetylmorphine
and Morphine over Heroin |
title_sort | development of
an effective monoclonal antibody against
heroin and its metabolites reveals therapies have mistargeted 6-monoacetylmorphine
and morphine over heroin |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9615117/ https://www.ncbi.nlm.nih.gov/pubmed/36313156 http://dx.doi.org/10.1021/acscentsci.2c00977 |
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