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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

neonatal abstinence syndrome (NAS) --- drug abuse and addiction --- editorial --- newborn --- drug withdrawal symptoms

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Paediatric medicine --- neonatal abstinence syndrome (NAS) --- drug abuse and addiction --- editorial --- newborn --- drug withdrawal symptoms --- neonatal abstinence syndrome (NAS) --- drug abuse and addiction --- editorial --- newborn --- drug withdrawal symptoms

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The book highlights important aspects of Molecular Psychiatry, including molecular mechanisms, animal models, biomarkers, advanced methods, drugs and antidepressant response, as well as genetics and epigenetics. Molecular mechanisms are a vital part of the search for the biological basis of psychiatric disorders, providing molecular hints that can later be tested as biomarkers or targets for drug development. Animal models represent a commonly used approach to aid in this bench-to-bed translation; the examples here are social defeat stress and the Roman High-Avoidance (RHA) and the Roman Low-Avoidance (RLA) rats. For biomarkers, psychiatric disorders pose a particular challenge due to the tissue specificity of many currently investigated biomarkers; i.e., not all blood-based measures directly represent changes in the brain. The Ebook includes five articles focused on the challenges of identifying clinically and biologically relevant biomarkers for psychiatric disorders. Scientific progress typically is fostered by the development of new methods. The application of machine learning methods for the proper analysis of Big Data and induced pluripotent stem cells are examples outlined in this Ebook. Furthermore, three articles are devoted to the understanding of the mechanisms of actions of existing drugs with the ultimate goal of identifying ways to predict treatment response in patients. Finally, three articles deepen the insight into the genetics and epigenetics of psychiatric disorders.

Medicine --- Mental health services --- cardiovascular disease --- cell adhesion molecules --- immunology --- inflammation --- nervous system --- schizophrenia --- bipolar disorder --- major depressive disorder --- DNA methylation --- response variability --- antipsychotics --- drug design --- multi-target drugs --- polypharmacology --- multi-task learning --- machine learning --- biomarker discovery --- psychiatry --- serotonin --- 5-HT 4 receptor --- 5-HT4R --- depression --- mood disorder --- expression --- Alzheimer's disease --- cognition --- Parkinson's disease --- forced swimming --- Roman rat lines --- stress --- hippocampus --- BDNF --- trkB --- PSA-NCAM --- western blot --- immunohistochemistry --- general cognitive function --- intelligence --- GWAS --- genetic correlation --- childhood-onset schizophrenia (COS) --- induced pluripotent stem cell (iPSC) --- copy number variation (CNV) --- early neurodevelopment --- neuronal differentiation --- synapse --- dendritic arborization --- miRNAs --- stress physiology --- cytoskeleton --- actin dynamics --- DRR1 --- TU3A --- FAM107A --- acid sphingomyelinase --- alcohol dependence --- liver enzymes --- sphingolipid metabolism --- withdrawal --- Hsp90 --- GR --- stress response --- steroid hormones --- molecular chaperones --- psychiatric disease --- circadian rhythms --- FKBP51 --- FKBP52 --- CyP40 --- PP5 --- DISC1 --- neurodevelopment --- CRMP-2 --- proteomics --- antidepressant treatment --- HPA axis --- gene expression --- FKBP5 --- sleep --- sleep EEG --- biomarkers --- antidepressants --- cordance --- gender --- sex difference --- antidepressant --- rapid-acting --- Ketamine --- endocrinology --- (2R,6R)-Hydroxynorketamine --- electroconvulsive therapy --- basic-helix-loop-helix --- brain --- coactivator --- glucocorticoids --- mineralocorticoid receptor knockout --- transcription biology --- dopaminergic gene polymorphisms --- affective temperament --- obesity --- alpha-synuclein --- SNCA --- major depression --- Hamilton Scale of Depression --- chemokines --- neuroinflammation --- social defeat --- Immune response --- T cells --- susceptibility --- resilience --- Treg cells --- Th17 cells --- behavior --- PPARγ --- cardiovascular disease --- cell adhesion molecules --- immunology --- inflammation --- nervous system --- schizophrenia --- bipolar disorder --- major depressive disorder --- DNA methylation --- response variability --- antipsychotics --- drug design --- multi-target drugs --- polypharmacology --- multi-task learning --- machine learning --- biomarker discovery --- psychiatry --- serotonin --- 5-HT 4 receptor --- 5-HT4R --- depression --- mood disorder --- expression --- Alzheimer's disease --- cognition --- Parkinson's disease --- forced swimming --- Roman rat lines --- stress --- hippocampus --- BDNF --- trkB --- PSA-NCAM --- western blot --- immunohistochemistry --- general cognitive function --- intelligence --- GWAS --- genetic correlation --- childhood-onset schizophrenia (COS) --- induced pluripotent stem cell (iPSC) --- copy number variation (CNV) --- early neurodevelopment --- neuronal differentiation --- synapse --- dendritic arborization --- miRNAs --- stress physiology --- cytoskeleton --- actin dynamics --- DRR1 --- TU3A --- FAM107A --- acid sphingomyelinase --- alcohol dependence --- liver enzymes --- sphingolipid metabolism --- withdrawal --- Hsp90 --- GR --- stress response --- steroid hormones --- molecular chaperones --- psychiatric disease --- circadian rhythms --- FKBP51 --- FKBP52 --- CyP40 --- PP5 --- DISC1 --- neurodevelopment --- CRMP-2 --- proteomics --- antidepressant treatment --- HPA axis --- gene expression --- FKBP5 --- sleep --- sleep EEG --- biomarkers --- antidepressants --- cordance --- gender --- sex difference --- antidepressant --- rapid-acting --- Ketamine --- endocrinology --- (2R,6R)-Hydroxynorketamine --- electroconvulsive therapy --- basic-helix-loop-helix --- brain --- coactivator --- glucocorticoids --- mineralocorticoid receptor knockout --- transcription biology --- dopaminergic gene polymorphisms --- affective temperament --- obesity --- alpha-synuclein --- SNCA --- major depression --- Hamilton Scale of Depression --- chemokines --- neuroinflammation --- social defeat --- Immune response --- T cells --- susceptibility --- resilience --- Treg cells --- Th17 cells --- behavior --- PPARγ

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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.

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

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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.

Medicine --- 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 --- 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