Opioids and Their Receptors

The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors repre...

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Julkaistu: MDPI - Multidisciplinary Digital Publishing Institute 2021
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collection Directory of Open Access Books
description The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors represent key milestones in opioid research. The opioid system modulates numerous pharmacological responses, with therapeutic (i.e., analgesia) and detrimental side effects (i.e., addiction). The medical use and misuse of opioids have dramatically increased, leading to the 21st century opioid crisis. This book presents recent developments in opioid drug discovery, specifically in the medicinal chemistry and pharmacology of new ligands targeting the opioid receptors as effective and safe therapeutics for human diseases. Furthermore, it draws a special attention to advancing concepts and strategies in opioid drug discovery to mitigate opioid liabilities. The diversity among the discussed topics is a testimony to the complexity of the opioid system, which results from the expression, regulation, and functional role of ligands and receptors. The array of multidisciplinary research areas illustrates the rapidly developing basic research and translational activities in opioid drug discovery. This book will serve as a useful reference while also stimulating continued research in the chemistry and pharmacology of opioids and their receptors, with the prospect of developing improved therapies for human diseases, but also improving health and quality of life in general.
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spelling doab-20.500.12854ir-694282024-03-30T23:22:42Z Opioids and Their Receptors Spetea, Mariana Schmidhammer, Helmut opioid receptors neurokinin-1 receptor peptide synthesis receptor binding studies functional assay writhing test tolerance Leu-enkephalin beta-arrestin mu opioid receptor delta opioid receptor biased signaling DADLE ischemia plasma stability morphinan BNTX δ opioid receptor antagonist 1H-NMR experiments mechanism elucidation peripheral antinociception 14-methoxycodeine-6-O-sulfate codeine-6-O-sulfate opioid peptides and peptidomimetics DAMGO DALDA [Dmt1]DALDA KGOP01 binding molecular docking structure-activity relationships β2-amino acids β2-Homo-amino acids µ-opioid receptor opioid peptides TAPP racemic synthesis of β2-amino acids peripheral µ-opioid receptors analgesia peripheral analgesic tolerance dysbiosis opioid bifunctional ligands (−)-N-phenethylnorhydromorphone analogs [35S]GTPgammaS assay forskolin-induced cAMP accumulation assays β-arrestin recruitment assays MOR and DOR agonists respiratory depression bias factor molecular modeling &amp simulation δ opioid receptor NTI derivative sulfonamide inverse agonist neutral antagonist agonist opioids mu receptor opioid side effects biased agonism partial agonism zerumbone chronic constriction injury (CCI) allodynia hyperalgesia potassium channels over-the-counter drugs misuse abuse opioid drugs pharmacology codeine dihydrocodeine loperamide opioid peptide macrocyclic tetrapeptide multifunctional ligands kappa opioid receptor analgesics opioid liabilities μ opioid receptor receptor model biased ligands dependence pain therapy neonatal opioid withdrawal syndrome naltrexone 6β-naltrexol buprenorphine G-protein bias arrestin recruitment respiration mitragynine heteromer internalization primary hippocampal culture lysosomes µ opioid receptor molecular dynamics docking interaction fingerprints biased agonists SR-17018 PZM21 morphine fentanyl diphenethylamines design and synthesis structure–activity relationships partial agonist biased agonist antagonist binding affinity selectivity n/a thema EDItEUR::M Medicine and Nursing The interest in opioids such as morphine, the prototypical opioid ligand, has been maintained through the years. The identification of endogenous opioids and their receptors (mu, delta, kappa, and nociceptin), molecular cloning, and the elucidation of the crystal structures of opioid receptors represent key milestones in opioid research. The opioid system modulates numerous pharmacological responses, with therapeutic (i.e., analgesia) and detrimental side effects (i.e., addiction). The medical use and misuse of opioids have dramatically increased, leading to the 21st century opioid crisis. This book presents recent developments in opioid drug discovery, specifically in the medicinal chemistry and pharmacology of new ligands targeting the opioid receptors as effective and safe therapeutics for human diseases. Furthermore, it draws a special attention to advancing concepts and strategies in opioid drug discovery to mitigate opioid liabilities. The diversity among the discussed topics is a testimony to the complexity of the opioid system, which results from the expression, regulation, and functional role of ligands and receptors. The array of multidisciplinary research areas illustrates the rapidly developing basic research and translational activities in opioid drug discovery. This book will serve as a useful reference while also stimulating continued research in the chemistry and pharmacology of opioids and their receptors, with the prospect of developing improved therapies for human diseases, but also improving health and quality of life in general. 2021-05-01T15:49:24Z 2021-05-01T15:49:24Z 2020 book ONIX_20210501_9783036500461_1174 9783036500461 9783036500478 https://directory.doabooks.org/handle/20.500.12854/69428 eng application/octet-stream Attribution 4.0 International https://mdpi.com/books/pdfview/book/3230 https://mdpi.com/books/pdfview/book/3230 MDPI - Multidisciplinary Digital Publishing Institute 10.3390/books978-3-03650-047-8 10.3390/books978-3-03650-047-8 46cabcaa-dd94-4bfe-87b4-55023c1b36d0 9783036500461 9783036500478 358 Basel, Switzerland open access
spellingShingle opioid receptors
neurokinin-1 receptor
peptide synthesis
receptor binding studies
functional assay
writhing test
tolerance
Leu-enkephalin
beta-arrestin
mu opioid receptor
delta opioid receptor
biased signaling
DADLE
ischemia
plasma stability
morphinan
BNTX
δ opioid receptor antagonist
1H-NMR experiments
mechanism elucidation
peripheral antinociception
14-methoxycodeine-6-O-sulfate
codeine-6-O-sulfate
opioid peptides and peptidomimetics
DAMGO
DALDA
[Dmt1]DALDA
KGOP01
binding
molecular docking
structure-activity relationships
β2-amino acids
β2-Homo-amino acids
µ-opioid receptor
opioid peptides
TAPP
racemic synthesis of β2-amino acids
peripheral µ-opioid receptors
analgesia
peripheral analgesic tolerance
dysbiosis
opioid
bifunctional ligands
(−)-N-phenethylnorhydromorphone analogs
[35S]GTPgammaS assay
forskolin-induced cAMP accumulation assays
β-arrestin recruitment assays
MOR and DOR agonists
respiratory depression
bias factor
molecular modeling &amp
simulation
δ opioid receptor
NTI derivative
sulfonamide
inverse agonist
neutral antagonist
agonist
opioids
mu receptor
opioid side effects
biased agonism
partial agonism
zerumbone
chronic constriction injury (CCI)
allodynia
hyperalgesia
potassium channels
over-the-counter drugs
misuse
abuse
opioid drugs
pharmacology
codeine
dihydrocodeine
loperamide
opioid peptide
macrocyclic tetrapeptide
multifunctional ligands
kappa opioid receptor
analgesics
opioid liabilities
μ opioid receptor
receptor model
biased ligands
dependence
pain therapy
neonatal opioid withdrawal syndrome
naltrexone
6β-naltrexol
buprenorphine
G-protein bias
arrestin recruitment
respiration
mitragynine
heteromer
internalization
primary hippocampal culture
lysosomes
µ opioid receptor
molecular dynamics
docking
interaction fingerprints
biased agonists
SR-17018
PZM21
morphine
fentanyl
diphenethylamines
design and synthesis
structure–activity relationships
partial agonist
biased agonist
antagonist
binding affinity
selectivity
n/a
thema EDItEUR::M Medicine and Nursing
Opioids and Their Receptors
title Opioids and Their Receptors
title_full Opioids and Their Receptors
title_fullStr Opioids and Their Receptors
title_full_unstemmed Opioids and Their Receptors
title_short Opioids and Their Receptors
title_sort opioids and their receptors
topic opioid receptors
neurokinin-1 receptor
peptide synthesis
receptor binding studies
functional assay
writhing test
tolerance
Leu-enkephalin
beta-arrestin
mu opioid receptor
delta opioid receptor
biased signaling
DADLE
ischemia
plasma stability
morphinan
BNTX
δ opioid receptor antagonist
1H-NMR experiments
mechanism elucidation
peripheral antinociception
14-methoxycodeine-6-O-sulfate
codeine-6-O-sulfate
opioid peptides and peptidomimetics
DAMGO
DALDA
[Dmt1]DALDA
KGOP01
binding
molecular docking
structure-activity relationships
β2-amino acids
β2-Homo-amino acids
µ-opioid receptor
opioid peptides
TAPP
racemic synthesis of β2-amino acids
peripheral µ-opioid receptors
analgesia
peripheral analgesic tolerance
dysbiosis
opioid
bifunctional ligands
(−)-N-phenethylnorhydromorphone analogs
[35S]GTPgammaS assay
forskolin-induced cAMP accumulation assays
β-arrestin recruitment assays
MOR and DOR agonists
respiratory depression
bias factor
molecular modeling &amp
simulation
δ opioid receptor
NTI derivative
sulfonamide
inverse agonist
neutral antagonist
agonist
opioids
mu receptor
opioid side effects
biased agonism
partial agonism
zerumbone
chronic constriction injury (CCI)
allodynia
hyperalgesia
potassium channels
over-the-counter drugs
misuse
abuse
opioid drugs
pharmacology
codeine
dihydrocodeine
loperamide
opioid peptide
macrocyclic tetrapeptide
multifunctional ligands
kappa opioid receptor
analgesics
opioid liabilities
μ opioid receptor
receptor model
biased ligands
dependence
pain therapy
neonatal opioid withdrawal syndrome
naltrexone
6β-naltrexol
buprenorphine
G-protein bias
arrestin recruitment
respiration
mitragynine
heteromer
internalization
primary hippocampal culture
lysosomes
µ opioid receptor
molecular dynamics
docking
interaction fingerprints
biased agonists
SR-17018
PZM21
morphine
fentanyl
diphenethylamines
design and synthesis
structure–activity relationships
partial agonist
biased agonist
antagonist
binding affinity
selectivity
n/a
thema EDItEUR::M Medicine and Nursing
topic_facet opioid receptors
neurokinin-1 receptor
peptide synthesis
receptor binding studies
functional assay
writhing test
tolerance
Leu-enkephalin
beta-arrestin
mu opioid receptor
delta opioid receptor
biased signaling
DADLE
ischemia
plasma stability
morphinan
BNTX
δ opioid receptor antagonist
1H-NMR experiments
mechanism elucidation
peripheral antinociception
14-methoxycodeine-6-O-sulfate
codeine-6-O-sulfate
opioid peptides and peptidomimetics
DAMGO
DALDA
[Dmt1]DALDA
KGOP01
binding
molecular docking
structure-activity relationships
β2-amino acids
β2-Homo-amino acids
µ-opioid receptor
opioid peptides
TAPP
racemic synthesis of β2-amino acids
peripheral µ-opioid receptors
analgesia
peripheral analgesic tolerance
dysbiosis
opioid
bifunctional ligands
(−)-N-phenethylnorhydromorphone analogs
[35S]GTPgammaS assay
forskolin-induced cAMP accumulation assays
β-arrestin recruitment assays
MOR and DOR agonists
respiratory depression
bias factor
molecular modeling &amp
simulation
δ opioid receptor
NTI derivative
sulfonamide
inverse agonist
neutral antagonist
agonist
opioids
mu receptor
opioid side effects
biased agonism
partial agonism
zerumbone
chronic constriction injury (CCI)
allodynia
hyperalgesia
potassium channels
over-the-counter drugs
misuse
abuse
opioid drugs
pharmacology
codeine
dihydrocodeine
loperamide
opioid peptide
macrocyclic tetrapeptide
multifunctional ligands
kappa opioid receptor
analgesics
opioid liabilities
μ opioid receptor
receptor model
biased ligands
dependence
pain therapy
neonatal opioid withdrawal syndrome
naltrexone
6β-naltrexol
buprenorphine
G-protein bias
arrestin recruitment
respiration
mitragynine
heteromer
internalization
primary hippocampal culture
lysosomes
µ opioid receptor
molecular dynamics
docking
interaction fingerprints
biased agonists
SR-17018
PZM21
morphine
fentanyl
diphenethylamines
design and synthesis
structure–activity relationships
partial agonist
biased agonist
antagonist
binding affinity
selectivity
n/a
thema EDItEUR::M Medicine and Nursing
url ONIX_20210501_9783036500461_1174