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Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics

Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro an...

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Detalles Bibliográficos
Autor principal: Goldberg, Joel S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Libertas Academica 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153123/
https://www.ncbi.nlm.nih.gov/pubmed/21863129
http://dx.doi.org/10.4137/PMC.S6803
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author Goldberg, Joel S.
author_facet Goldberg, Joel S.
author_sort Goldberg, Joel S.
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description Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski’s criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research.
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spelling pubmed-31531232011-08-23 Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics Goldberg, Joel S. Perspect Medicin Chem Perspective Low molecular weight opioid peptide esters (OPE) could become a class of analgesics with different side effect profiles than current opiates. OPE may have sufficient plasma stability to cross the blood brain barrier (BBB), undergo ester hydrolysis and produce analgesia. OPE of dipeptides, tyr-pro and tyr-gly conjugated to ethanol have a structure similar to the anesthestic agent, etomidate. Based upon the analgesic activity of dipeptide opioids, Lipinski’s criteria, and permeability of select GABA esters to cross the BBB, opioid peptides (OP) conjugated to ethanol, cholesterol or 3-glucose are lead recommendations. Preliminary animal data suggests that tyr-pro-ethyl ester crosses the BBB and unexpectedly produces hyperalgesia. Currently, there are no approved OP analgesics available for clinical use. Clinical trials of good manufacturing practice OP administered to patients suffering from chronic pain with indwelling intrathecal pumps could resolve the issue that OP may be superior to opiates and may redirect research. Libertas Academica 2011-07-25 /pmc/articles/PMC3153123/ /pubmed/21863129 http://dx.doi.org/10.4137/PMC.S6803 Text en © the author(s), publisher and licensee Libertas Academica Ltd. This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
spellingShingle Perspective
Goldberg, Joel S.
Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics
title Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics
title_full Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics
title_fullStr Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics
title_full_unstemmed Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics
title_short Low Molecular Weight Opioid Peptide Esters Could be Developed as a New Class of Analgesics
title_sort low molecular weight opioid peptide esters could be developed as a new class of analgesics
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153123/
https://www.ncbi.nlm.nih.gov/pubmed/21863129
http://dx.doi.org/10.4137/PMC.S6803
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