PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression

Pharmacological Research, Год журнала: 2024, Номер 206, С. 107300 - 107300

Опубликована: Июль 9, 2024

Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.

Язык: Английский

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Novel Pyridine Derivatives as 5-HT2A Agonists for Treating Psychiatric Disorders

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер 16(2), С. 192 - 193

Опубликована: Янв. 8, 2025

Provided herein are novel pyridine derivatives as 5-HT2A agonists, pharmaceutical compositions, use of such compounds in treating psychiatric disorders, and processes for preparing compounds.

Язык: Английский

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Novel 3-Pyrrolidineindole Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis and Mental Illnesses Such as Depression and Post-Traumatic Stress Disorder

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 16(1), С. 18 - 19

Опубликована: Дек. 10, 2024

Provided herein are novel 3-pyrrolidineindole derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis and mental illnesses depression post-traumatic stress disorder, processes for preparing compounds.

Язык: Английский

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Multi-detection of seratonin and dopamine based on an electrochemical aptasensor

Chemical Papers, Год журнала: 2024, Номер 78(12), С. 7175 - 7185

Опубликована: Июль 20, 2024

Язык: Английский

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Impact of gene-by-trauma interaction in MDD-related multimorbidity clusters

Journal of Affective Disorders, Год журнала: 2024, Номер 359, С. 382 - 391

Опубликована: Май 26, 2024

Major depressive disorder (MDD) is considerably heterogeneous in terms of comorbidities, which may hamper the disentanglement its biological mechanism. In a previous study, we classified lifetime trajectories MDD-related multimorbidities into seven distinct clusters, each characterized by unique genetic and environmental risk-factor profiles. The current objective was to investigate genome-wide gene-by-environment (G × E) interactions with childhood trauma burden, within context these clusters.

Язык: Английский

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Novel Ergoline Compounds as 5-HT2A Agonists for Treating Mood Disorders Such as Depressive Disorders and Bipolar Disorders

ACS Medicinal Chemistry Letters, Год журнала: 2024, Номер 16(1), С. 32 - 33

Опубликована: Дек. 20, 2024

Provided herein are novel ergoline compounds as 5-HT2A agonists, pharmaceutical compositions, use of such in treating mood disorders depressive and bipolar disorders, processes for preparing compounds.

Язык: Английский

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Novel 3-Cycloaminoindole Compounds as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness, and CNS Disorders

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер 16(2), С. 190 - 191

Опубликована: Янв. 4, 2025

Provided herein are novel 3-cycloaminoindole compounds as serotonergic psychedelic agents, pharmaceutical compositions, use of such in treating psychosis, mental illness and central nervous system (CNS) disorders processes for preparing compounds.

Язык: Английский

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Novel Pyrrolopyridine Compounds as 5-HT2A Agonists for Treating Mental Illnesses

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер 16(2), С. 202 - 203

Опубликована: Янв. 23, 2025

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightJanuary 23, 2025Novel Pyrrolopyridine Compounds as 5-HT2A Agonists for Treating Mental IllnessesClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia 30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Anika R. SabnisAnika SabnisDepartment of Neurosurgery, Icahn School Medicine at Mount Sinai, New York, York 10029, StatesMore Anika SabnisOpen PDFACS LettersCite this: Med. Chem. Lett. 2025, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00019https://doi.org/10.1021/acsmedchemlett.5c00019Published January 2025 Publication History Received 12 2025Published online 23 2025editorialPublished American Chemical Society. available under these Terms Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel pyrrolopyridine compounds agonists, pharmaceutical compositions, use such in treating mental illnesses, processes preparing compounds.This licensed personal The PublicationsPublished SocietySpecial IssuePublished part Letters special issue "Psychedelics Entactogens". Important Compound Classes TitlePyrrolopyridine the Treatment Illnesses NumberWO 2025/000051 A1URL: https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025000051&_cid=P12-M5TW4S-73441-1 DateJanuary 2, Priority ApplicationAU 2023902053 DateJune 28, 2023 InventorsBanister, S.; Jorgensen, W.; Tan, J.; Whish, L. Assignee CompanyPsylo Pty Ltd., Australia Disease AreaMental illnesses Biological Target5-HT2A SummaryMental illness covers many neuropsychiatric disorders which an enormous burden lives their sufferers. Diagnoses treatment-resistant depression, major depressive disorders, eating substance abuse post-traumatic stress disorder, obsessive compulsive attention deficit schizophrenia, others can cause devastating symptoms that sufferers lose ability lead a normal life.Psychedelics (serotonergic hallucinogens) powerful psychoactive substances alter perception mood affect numerous cognitive processes. After discovery (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD) identification serotonin brain, early research focused intensively on LSD. Today, there consensus psychedelics agonists or partial brain 5-hydroxytryptamine 2A (5-HT2A) receptors. Psychedelics have both rapid onset persisting effects, include changes function. classical psychotic agents LSD, psilocybin, mescaline.The receptor plays important role emotional responses target be considered action agonist psychedelics. In fact, majority known produce hallucinogenic effects humans. Psilocybin activates 5HT1A receptors, may contribute antidepressant/antianxiety effects.Psychosis often referred abnormal state mind characterized hallucinatory experiences, delusional thinking, disordered thoughts. Anecdotal evidence suggests low, nonhallucinogenic doses reduce schizophrenia psychosis.The present application describes series treatment illnesses. Further, discloses compounds, preparation, use, composition, treatment. DefinitionsR1 = H, C1–C6 alkyl, haloalkyl, C2–C6 alkenyl, haloalkenyl, alkynyl, haloalkynyl, C3–C8 cycloalkyl, C4–C14 alkylenecycloalkyl, heterocycloalkyl, alkyleneheterocycloalkyl, C6–C12 aryl, C7–C18 alkylenearyl, C5–C10 heteroaryl, C6–C16 alkyleneheteroaryl;R2 alkyleneheteroaryl;R3 alkylenecycloalkyl; andR7, R8, R9, R10, R11 halogen, CN, OR13, N(R13)2, SR13, alkylamine, alkoxy, haloalkoxy, CO2R13. Key Structures AssayThe FLIPR Ca2+ flux functional assay was performed. described were tested activity receptor. EC50 values (nM) shown following table. DataThe table below shows representative biological data obtained from testing examples. ClaimsTotal claims: 23Compound 16Pharmaceutical composition 1Method 4Use compound 1Medicament 1 Recent Review ArticlesSee refs (1−6).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]AuthorAnika Department StatesNotesThe authors declare no competing financial interest.ReferencesClick copied! references 6 other publications. 1Duan, Cao, D.; Wang, Cheng, J. Serotonin Receptor (5-HT R) Agonists: Non-Hallucinogenic Analogues Emerging Antidepressants. Rev. 2024, 124, 124– 163, DOI: 10.1021/acs.chemrev.3c00375 Google ScholarThere corresponding record reference.2Miranda, Antidepressant anxiolytic activating 5HT2A receptors anterior cingulate cortex theoretical mechanisms underlying them – A scoping review literature. Brain Res. 1846, 149226, 10.1016/j.brainres.2024.149226 reference.3Glennon, A.; Dukat, M. 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From Obscure Pivotal Member DOX Family Serotonergic Psychedelic Agents Review. Pharmacol. Transl. Sci. 7, 1722– 1745, 10.1021/acsptsci.4c00157 reference.4Korkmaz, N. Cikrikcili, U.; Akan, M.; Yucesan, E. therapy depression disorders. Eur. Neurosci. 60, 4063– 4077, 10.1111/ejn.16421 reference.5Sabnis, Novel 3-Pyrrolidineindole Derivatives Psychosis Such Depression Post-Traumatic Stress Disorder. 16, 18– 19, 10.1021/acsmedchemlett.4c00581 reference.6Bremshey, Groß, Renken, K.; Masseck, O. A. depression─A historical roundup future directions. Neurochem. 168, 1751– 1779, 10.1111/jnc.16097 reference.Cited By Click copied!This has not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.5c00019Published permissionsArticle Views-Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since November 2008 (both PDF HTML) across all institutions individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find more information counts.The Altmetric Attention Score quantitative measure received online. Clicking donut icon will load page altmetric.com with additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Язык: Английский

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Novel Indoline Derivatives as Serotonergic Psychedelic Agents for Treating Psychosis, Mental Illness and CNS Disorders

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер 16(2), С. 196 - 197

Опубликована: Янв. 23, 2025

Provided herein are novel indoline derivatives as serotonergic psychedelic agents, pharmaceutical compositions, use of such compounds in treating psychosis, mental illness and central nervous system (CNS) disorders processes for preparing compounds.

Язык: Английский

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Novel Compounds as 5-HT2A Agonists for Treating Mental Illness or CNS Disorders

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер 16(3), С. 377 - 378

Опубликована: Фев. 11, 2025

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightFebruary 11, 2025Novel Compounds as 5-HT2A Agonists for Treating Mental Illness or CNS DisordersClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia 30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Anika R. SabnisAnika SabnisDepartment of Neurosurgery, Icahn School Medicine at Mount Sinai, New York, York 10029, StatesMore Anika SabnisOpen PDFACS LettersCite this: Med. Chem. Lett. 2025, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00066https://doi.org/10.1021/acsmedchemlett.5c00066Published February 2025 Publication History Received 2 2025Published online 11 2025editorialPublished American Chemical Society. available under these Terms Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel compounds agonists, pharmaceutical compositions, use such in treating mental illness disorders processes preparing compounds.This licensed personal The PublicationsPublished SocietySpecial IssuePublished part Letters special issue "Psychedelics Entactogens". Important Compound Classes TitleCompounds NumberWO 2025/000053 A1 URLhttps://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025000053&_cid=P12-M6MQMA-76721-1 DateJanuary 2, Priority ApplicationAU 2023902054 DateJune 28, 2023 InventorsBanister, S.; Jorgensen, W.; Tan, J.; Whish, L. Assignee CompanyPsylo Pty Ltd., Australia Disease AreaMental Biological Target5-HT2A SummaryMental covers many neuropsychiatric that cause enormous burden the lives their sufferers. Diagnoses treatment resistant depression, major depressive disorders, eating substance abuse post-traumatic stress disorder, obsessive compulsive attention deficit schizophrenia, others can devastating symptoms sufferers lose capability leading a normal life.Psychedelics (serotonergic hallucinogens) powerful psychoactive substances alter perception mood affect numerous cognitive processes. After discovery (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD) identification serotonin brain, early research focused intensively on LSD. Today, there consensus psychedelics agonists partial brain 5-hydroxytryptamine 2A (5-HT2A) receptors. Psychedelics have both rapid onset persisting effects, which includes changes function. classical psychotic agents include LSD, psilocybin, mescaline.The receptor plays an important role emotional responses target be considered action agonist psychedelics. In fact, majority known produce hallucinogenic effects humans. Psilocybin activates 5HT1A receptors, may contribute antidepressant/antianxiety effects.Psychosis often referred abnormal state mind characterized hallucinatory experiences, delusional thinking disordered thoughts. Anecdotal evidence suggests low, nonhallucinogenic doses reduce schizophrenia psychosis.The present application describes series central nervous system (CNS) disorders. Further, discloses compounds, preparation, use, composition, treatment. DefinitionsR1 = H, C1–C6 alkyl, haloalkyl, C2–C6 alkenyl, haloalkenyl, alkynyl, haloalkynyl, C3–C8 cycloalkyl, C4–C14 alkylenecycloalkyl, heterocycloalkyl, alkyleneheterocycloalkyl, C6–C12 aryl, C7–C18 alkylenearyl, C5–C10 heteroaryl, C6–C16 alkyleneheteroaryl;R2 alkyleneheteroaryl;R3 alkylenecycloalkyl;L C1–C4 alkylene, C2–C4 alkenylene, alkynylene;Z1 CR8 N; Z2 CR9 Z3 CR10 Z4 CR11 andR6 alkyleneP(O)(OR12)2, C(O)R12, CO2R12, C(O)N(R12)2, S(O)R12, SO2R12. Key Structures AssayThe FLIPR Ca2+ flux functional assay was performed. described were tested activity receptor. EC50 (nM) shown following Table. DataTable below shows representative 5-HT2A. biological data obtained from testing examples listed ClaimsTotal claims: 23Compound 14Pharmaceutical composition 1Method 7Medicament 1 Recent Review ArticlesSee refs (1−6).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]AuthorAnika Department StatesNotesThe authors declare no competing financial interest.ReferencesClick copied! references 6 other publications. 1Duan, Cao, D.; Wang, Cheng, J. Serotonin Receptor (5-HT2AR) Agonists: Non-Hallucinogenic Analogues Emerging Antidepressants. Rev. 2024, 124, 124– 163, DOI: 10.1021/acs.chemrev.3c00375 Google ScholarThere corresponding record reference.2Miranda, Antidepressant anxiolytic activating 5HT2A receptors anterior cingulate cortex theoretical mechanisms underlying them─A scoping review literature. Brain Res. 1846, 149226, 10.1016/j.brainres.2024.149226 reference.3Glennon, A.; Dukat, M. 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From Obscure Pivotal Member DOX Family Serotonergic Psychedelic Agents─A Review. Pharmacol. Transl. Sci. 7, 1722– 1745, 10.1021/acsptsci.4c00157 reference.4Korkmaz, N. Cikrikcili, U.; Akan, M.; Yucesan, E. therapy depression Eur. Neurosci. 60, 4063– 4077, 10.1111/ejn.16421 reference.5Sabnis, Novel 3-Pyrrolidineindole Derivatives Agents Psychosis Illnesses Such Depression Post-Traumatic Stress Disorder. 16, 18– 19, 10.1021/acsmedchemlett.4c00581 reference.6Bremshey, Grob, Renken, K.; Masseck, O. A. depression─A historical roundup future directions. Neurochem. 168, 1751– 1779, 10.1111/jnc.16097 reference.Cited By Click copied!This has not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.5c00066Published permissionsArticle Views-Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since November 2008 (both PDF HTML) across all institutions individuals. These regularly updated reflect usage up last few days.Citations number articles citing article, calculated Crossref daily. Find more information counts.The Altmetric Attention Score quantitative measure received online. Clicking donut icon will load page altmetric.com with additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Язык: Английский

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