Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Pharmaceutical Design
  4. Fast Track Articles
  5. Fast Track Article
image of Probing the Molecular Mechanisms of Kratom's Antipsychotic Effects through a Multi-modal Computational Approach

Abstract

Background

Psychosis, marked by detachment from reality, includes symptoms like hallucinations and delusions. Traditional herbal remedies like kratom are gaining attention for psychiatric conditions. This was aimed at comprehending the molecular mechanisms of Kratom's antipsychotic effects utilizing a multi-modal computational approach.

Materials and Methods

This study employed network pharmacology followed by molecular docking and molecular dynamics simulation study to investigate the potential antipsychotic properties of kratom compounds by identifying their key molecular targets and interactions.

Results

Compounds present in kratom interact with a variety of receptors and proteins that play a pivotal role in neurotransmission, neurodevelopment, and cellular signaling. These interactions, particularly with dopamine and serotonin receptors, various proteins, and pathways, suggest a complex influence on psychiatric conditions. Both mitragynine and zotepine (an atypical antipsychotic drug) display significant binding affinities for 5HTR2A receptors, suggesting their potential for modulating related physiological pathways. Mitragynine displayed higher flexibility in binding compared to zotepine, which showed a more stable interaction. Hydrogen bond analysis revealed a more variable interaction profile for mitragynine than zotepine.

Conclusion

The research findings suggest that the interaction between kratom compounds and essential brain receptors could influence psychiatric conditions. Notably, both mitragynine (a key kratom component) and zotepine (an antipsychotic) bind to the 5HTR2A receptor, suggesting the potential for kratom to modulate similar pathways. Interestingly, mitragynine's flexible binding mode compared to zotepine might indicate a more diverse range of effects. Overall, the findings suggest complex interactions between kratom and the brain's signaling system, warranting further investigation into its potential therapeutic effects.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128335217241031033104
2025-01-01
2025-01-30

  • From This Site

    /content/journals/cpd/10.2174/0113816128335217241031033104
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Gaebel W. Zielasek J. Focus on psychosis. Dialogues Clin. Neurosci. 2015 17 1 9 18 10.31887/DCNS.2015.17.1/wgaebel 25987859
    [Google Scholar]
  2. Sisti D.A. Calkins M.E. Psychosis risk: What is it and how should we talk about it? AMA J. Ethics 2016 18 6 624 632 10.1001/journalofethics.2016.18.6.msoc1‑1606 27322996
    [Google Scholar]
  3. Kart A. Özdel K. Türkçapar H. Cognitive behavioral therapy in treatment of schizophrenia. Noro Psikiyatri Arsivi 2021 58 Suppl. 1 S61 S65 10.29399/npa.27418 34658637
    [Google Scholar]
  4. Falloon I.R.H. Boyd J.L. McGill C.W. Family Care of Schizophrenia: A Problem-solving Approach to the Treatment of Mental Illness New York The Guilford Press 1984
    [Google Scholar]
  5. Bach P. Hayes S.C. The use of acceptance and commitment therapy to prevent the rehospitalization of psychotic patients: A randomized controlled trial. J. Consult. Clin. Psychol. 2002 70 5 1129 1139 10.1037/0022‑006X.70.5.1129 12362963
    [Google Scholar]
  6. Drake R.E. Whitley R. Recovery and severe mental illness: description and analysis. Can. J. Psychiatry 2014 59 5 236 242 10.1177/070674371405900502 25007276
    [Google Scholar]
  7. Ee C. Lake J. Firth J. Hargraves F. de Manincor M. Meade T. Marx W. Sarris J. An integrative collaborative care model for people with mental illness and physical comorbidities. Int. J. Ment. Health Syst. 2020 14 1 83 10.1186/s13033‑020‑00410‑6 33292354
    [Google Scholar]
  8. Wemrell M. Olsson A. Landgren K. The use of complementary and alternative medicine (CAM) in psychiatric units in Sweden. Issues Ment. Health Nurs. 2020 41 10 946 957 10.1080/01612840.2020.1744203 32497455
    [Google Scholar]
  9. Berman S. Mischoulon D. Naidoo U. Complementary medicine and natural medications in psychiatry: A guide for the consultation-liaison psychiatrist. Psychosomatics 2020 61 5 508 517 10.1016/j.psym.2020.04.010 32460988
    [Google Scholar]
  10. Schulz P. Hede V. Alternative and complementary approaches in psychiatry: Beliefs versus evidence. Dialogues Clin. Neurosci. 2018 20 3 207 214 10.31887/DCNS.2018.20.3/pschulz 30581290
    [Google Scholar]
  11. Meireles V. Rosado T. Barroso M. Soares S. Gonçalves J. Luís Â. Caramelo D. Simão A.Y. Fernández N. Duarte A.P. Gallardo E. Mitragyna speciosa: Clinical, toxicological aspects and analysis in biological and non-biological samples. Medicines (Basel) 2019 6 1 35 10.3390/medicines6010035 30836609
    [Google Scholar]
  12. Eastlack S.C. Cornett E.M. Kaye A.D. Kratom - Pharmacology, clinical implications, and outlook: A comprehensive review. Pain Ther. 2020 9 1 55 69 10.1007/s40122‑020‑00151‑x 31994019
    [Google Scholar]
  13. Johnson L.E. Balyan L. Magdalany A. Saeed F. Salinas R. Wallace S. Veltri C.A. Swogger M.T. Walsh Z. Grundmann O. The potential for kratom as an antidepressant and antipsychotic. Yale J. Biol. Med. 2020 93 2 283 289 32607089
    [Google Scholar]
  14. Prevete E. Kuypers K.P.C. Theunissen E.L. Esposito G. Ramaekers J.G. Pasquini M. Corazza O. Clinical implications of kratom (Mitragyna speciosa) use: A literature review. Curr. Addict. Rep. 2023 10 2 317 334 10.1007/s40429‑023‑00478‑3 37266188
    [Google Scholar]
  15. National Narcotics Agency Analysis of Mitragynine in Kratom Leaf Powder in Several Marketed Kratom Variant Products Bogor BNN Narcotics Laboratory Center 2020
    [Google Scholar]
  16. Flores-Bocanegra L. Raja H.A. Graf T.N. Augustinović M. Wallace E.D. Hematian S. Kellogg J.J. Todd D.A. Cech N.B. Oberlies N.H. The chemistry of kratom [Mitragyna speciosa]: Updated characterization data and methods to elucidate indole and oxindole alkaloids. J. Nat. Prod. 2020 83 7 2165 2177 10.1021/acs.jnatprod.0c00257 32597657
    [Google Scholar]
  17. Veeramohan R. Azizan K.A. Aizat W.M. Goh H.H. Mansor S.M. Yusof N.S.M. Baharum S.N. Ng C.L. Metabolomics data of Mitragyna speciosa leaf using LC-ESI-TOF-MS. Data Brief 2018 18 1212 1216 10.1016/j.dib.2018.04.001 29900296
    [Google Scholar]
  18. Houghton P.J. Latiff A. Said I.M. Alkaloids from Mitragyna speciosa. Phytochemistry 1991 30 1 347 350 10.1016/0031‑9422(91)84152‑I
    [Google Scholar]
  19. Avula B. Sagi S. Wang Y.H. Wang M. Ali Z. Smillie T.J. Zweigenbaum J. Khan I.A. Identification and characterization of indole and oxindole alkaloids from leaves of mitragyna speciosa korth using liquid chromatography - Accurate QToF mass spectrometry. J. AOAC Int. 2015 98 1 13 21 10.5740/jaoacint.14‑110 25857873
    [Google Scholar]
  20. Szklarczyk D. Kirsch R. Koutrouli M. Nastou K. Mehryary F. Hachilif R. Gable A.L. Fang T. Doncheva N.T. Pyysalo S. Bork P. Jensen L.J. von Mering C. The STRING database in 2023: Protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 2023 51 D1 D638 D646 10.1093/nar/gkac1000 36370105
    [Google Scholar]
  21. Shannon P. Markiel A. Ozier O. Baliga N.S. Wang J.T. Ramage D. Amin N. Schwikowski B. Ideker T. Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 2003 13 11 2498 2504 10.1101/gr.1239303 14597658
    [Google Scholar]
  22. Sherman B.T. Hao M. Qiu J. Jiao X. Baseler M.W. Lane H.C. Imamichi T. Chang W. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022 50 W1 W216 W221 10.1093/nar/gkac194 35325185
    [Google Scholar]
  23. Khurana N. Ishar M.P.S. Gajbhiye A. Goel R.K. PASS assisted prediction and pharmacological evaluation of novel nicotinic analogs for nootropic activity in mice. Eur. J. Pharmacol. 2011 662 1-3 22 30 10.1016/j.ejphar.2011.04.048 21554868
    [Google Scholar]
  24. S P. Prediction of activity spectra for substances. J. Pharmacol. Pharmacother. 2011 2 1 52 53 10.4103/0976‑500X.77119 21701651
    [Google Scholar]
  25. McNutt A.T. Francoeur P. Aggarwal R. Masuda T. Meli R. Ragoza M. Sunseri J. Koes D.R. GNINA 1.0: Molecular docking with deep learning. J. Cheminform. 2021 13 1 43 10.1186/s13321‑021‑00522‑2 34108002
    [Google Scholar]
  26. Tallei T.E. Fatimawali Adam A.A. 2023 Molecular insights into the anti-inflammatory activity of fermented pineapple juice using multimodal computational studies. Arch Pharm (Weinheim) 357 7 e2300422 10.1002/ardp.202300422 37861276
    [Google Scholar]
  27. Abraham M.J. Murtola T. Schulz R. Páll S. Smith J.C. Hess B. Lindahl E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 2015 1-2 19 25 10.1016/j.softx.2015.06.001
    [Google Scholar]
  28. Wang Y. Joseph J. Gao Y. Hu B. Geng X. Wu D. Wang J. Zhang F. Revealing the interaction modes of 5-HT2A receptor antagonists and the structure-based virtual screening from FDA and TCMNP database. J. Biomol. Struct. Dyn. 2021 39 10 3681 3692 10.1080/07391102.2020.1768900 32406337
    [Google Scholar]
  29. Xiong G. Wu Z. Yi J. Fu L. Yang Z. Hsieh C. Yin M. Zeng X. Wu C. Lu A. Chen X. Hou T. Cao D. ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 2021 49 W1 W5 W14 10.1093/nar/gkab255 33893803
    [Google Scholar]
  30. Drwal M.N. Banerjee P. Dunkel M. Wettig M.R. Preissner R. ProTox: A web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res. 2014 42 W1 W53 W58 10.1093/nar/gku401 24838562
    [Google Scholar]
  31. Lipinski C.A. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discov. Today. Technol. 2004 1 4 337 341 10.1016/j.ddtec.2004.11.007 24981612
    [Google Scholar]
  32. Todd D.A. Kellogg J.J. Wallace E.D. Khin M. Flores-Bocanegra L. Tanna R.S. McIntosh S. Raja H.A. Graf T.N. Hemby S.E. Paine M.F. Oberlies N.H. Cech N.B. Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions. Sci. Rep. 2020 10 1 19158 10.1038/s41598‑020‑76119‑w 33154449
    [Google Scholar]
  33. Hossain R. Sultana A. Nuinoon M. Noonong K. Tangpong J. Hossain K.H. Rahman M.A. A critical review of the neuropharmacological effects of kratom: An insight from the functional array of identified natural compounds. Molecules 2023 28 21 7372 10.3390/molecules28217372 37959790
    [Google Scholar]
  34. Hanapi N.A. Chear N.J.Y. Azizi J. Yusof S.R. Kratom alkaloids: Interactions with enzymes, receptors, and cellular barriers. Front. Pharmacol. 2021 12 751656 10.3389/fphar.2021.751656 34867362
    [Google Scholar]
  35. Morris-Schaffer K. McCoy M.J. A review of the LD 50 and its current role in hazard communication. J. Chem. Health Saf. 2021 28 1 25 33 10.1021/acs.chas.0c00096
    [Google Scholar]
  36. Salvador J. Gutierrez G. Llavero M. Gargallo J. Escalada J. López J. Endocrine disorders and psychiatric manifestations. Endocrinol. Sys. Dis. 2019 1 35 10.1007/978‑3‑319‑66362‑3_12‑1
    [Google Scholar]
  37. Cabana-Domínguez J. Torrico B. Reif A. Fernàndez-Castillo N. Cormand B. Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders. Transl. Psychiatry 2022 12 1 11 10.1038/s41398‑021‑01771‑3 35013130
    [Google Scholar]
  38. Mata I. Arranz M.J. Patiño A. Lai T. Beperet M. Sierrasesumaga L. Serotonergic polymorphisms and psychotic disorders in populations from North Spain. Am. J. Med. Genet. B Neuropsychiatr. Genet. 126B 1 88 94 15048655 10.1002/ajmg.b.20150
    [Google Scholar]
  39. Quednow B.B. Geyer M.A. Halberstadt A.L. Serotonin and schizophrenia. Handb. Behav. Neurosci. 2010 21 585 620 10.1016/S1569‑7339(10)70102‑8
    [Google Scholar]
  40. Nascimento J.M. Saia-Cereda V.M. Zuccoli G.S. Reis-de-Oliveira G. Carregari V.C. Smith B.J. Rehen S.K. Martins-de-Souza D. Proteomic signatures of schizophrenia-sourced iPSC-derived neural cells and brain organoids are similar to patients’ postmortem brains. Cell Biosci. 2022 12 1 189 10.1186/s13578‑022‑00928‑x 36451159
    [Google Scholar]
  41. Antunes A.S.L.M. Reis-de-Oliveira G. Martins-de-Souza D. Molecular overlaps of neurological manifestations of COVID-19 and schizophrenia from a proteomic perspective. Eur. Arch. Psychiatry Clin. Neurosci. 2024 10.1007/s00406‑024‑01842‑8 39028452
    [Google Scholar]
  42. Mao Y. Fisher D.W. Yang S. Keszycki R.M. Dong H. Protein-protein interactions underlying the behavioral and psychological symptoms of dementia (BPSD) and Alzheimer’s disease. PLoS One 2020 15 1 e0226021 10.1371/journal.pone.0226021 31951614
    [Google Scholar]
  43. Rajalingam A. Ganjiwale A. Identification of common genetic factors and immune-related pathways associating more than two autoimmune disorders: Implications on risk, diagnosis, and treatment. Genomics Inform. 2024 22 1 10 10.1186/s44342‑024‑00004‑5 38956704
    [Google Scholar]
  44. Xia J. Benner M.J. Hancock R.E.W. NetworkAnalyst - Iintegrative approaches for protein–protein interaction network analysis and visual exploration. Nucleic Acids Res. 2014 42 W1 W167 W174 10.1093/nar/gku443 24861621
    [Google Scholar]
  45. Zhang X. Connelly J. Chao Y. Wang Q.J. Multifaceted functions of protein kinase D in pathological processes and human diseases. Biomolecules 2021 11 3 483 10.3390/biom11030483 33807058
    [Google Scholar]
  46. Du L. Wilson B.A.P. Li N. Shah R. Dalilian M. Wang D. Smith E.A. Wamiru A. Goncharova E.I. Zhang P. O’Keefe B.R. Discovery and synthesis of a naturally derived protein kinase inhibitor that selectively inhibits distinct classes of serine/threonine kinases. J. Nat. Prod. 2023 86 10 2283 2293 10.1021/acs.jnatprod.3c00394 37843072
    [Google Scholar]
  47. Van A.A.N. Kunkel M.T. Baffi T.R. Lordén G. Antal C.E. Banerjee S. Newton A.C. Protein kinase C fusion proteins are paradoxically loss of function in cancer. J. Biol. Chem. 2021 296 100445 https://doi.org/https://doi.org/10.1016/j.jbc.2021.100445 10.1016/j.jbc.2021.100445 33617877
    [Google Scholar]
  48. Colgan L.A. Hu M. Misler J.A. Parra-Bueno P. Moran C.M. Leitges M. Yasuda R. PKCα integrates spatiotemporally distinct Ca2+ and autocrine BDNF signaling to facilitate synaptic plasticity. Nat. Neurosci. 2018 21 8 1027 1037 10.1038/s41593‑018‑0184‑3 30013171
    [Google Scholar]
  49. Stevens C.F. Sullivan J.M. Regulation of the readily releasable vesicle pool by protein kinase C. Neuron 1998 21 4 885 893 https://doi.org/https://doi.org/10.1016/S0896-6273(00)80603-0 10.1016/S0896‑6273(00)80603‑0 9808473
    [Google Scholar]
  50. Zhou M.H. Chen S.R. Wang L. Huang Y. Deng M. Zhang J. Zhang J. Chen H. Yan J. Pan H.L. Protein kinase C-mediated phosphorylation and α2δ-1 interdependently regulate NMDA receptor trafficking and activity. J. Neurosci. 2021 41 30 6415 6429 10.1523/JNEUROSCI.0757‑21.2021 34252035
    [Google Scholar]
  51. Lallemend F. Hadjab S. Hans G. Moonen G. Lefebvre P.P. Malgrange B. Activation of protein kinase CβI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons. J. Cell Sci. 2005 118 19 4511 4525 10.1242/jcs.02572 16179609
    [Google Scholar]
  52. Noguès X. Protein kinase C, learning and memory: A circular determinism between physiology and behaviour. Prog. Neuropsychopharmacol. Biol. Psychiatry 1997 21 3 507 529 10.1016/S0278‑5846(97)00015‑8 9153070
    [Google Scholar]
  53. Oda Y. Kanahara N. Iyo M. Alterations of dopamine D2 receptors and related receptor-interacting proteins in schizophrenia: The pivotal position of dopamine supersensitivity psychosis in treatment-resistant schizophrenia. Int. J. Mol. Sci. 2015 16 12 30144 30163 10.3390/ijms161226228 26694375
    [Google Scholar]
  54. Quintana C. Beaulieu J.M. A fresh look at cortical dopamine D2 receptor expressing neurons. Pharmacol. Res. 2019 139 440 445 10.1016/j.phrs.2018.12.001 30528973
    [Google Scholar]
  55. Tung M.C. Lin Y.W. Lee W.J. Wen Y.C. Liu Y.C. Chen J.Q. Hsiao M. Yang Y.C. Chien M.H. Targeting DRD2 by the antipsychotic drug, penfluridol, retards growth of renal cell carcinoma via inducing stemness inhibition and autophagy-mediated apoptosis. Cell Death Dis. 2022 13 4 400 10.1038/s41419‑022‑04828‑3 35461314
    [Google Scholar]
  56. Feng S. Sun P. Qu C. Wu X. Yang L. Yang T. Wang S. Fang Y. Chen J. Exploring the core genes of schizophrenia based on bioinformatics analysis. Genes (Basel) 2022 13 6 967 10.3390/genes13060967 35741729
    [Google Scholar]
  57. Boyer E.W. Babu K.M. Adkins J.E. McCurdy C.R. Halpern J.H. Self‐treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction 2008 103 6 1048 1050 10.1111/j.1360‑0443.2008.02209.x 18482427
    [Google Scholar]
  58. Edinoff A.N. Swinford C.R. Odisho A.S. Burroughs C.R. Stark C.W. Raslan W.A. Cornett E.M. Kaye A.M. Kaye A.D. Clinically relevant drug interactions with monoamine oxidase inhibitors. Health Psychol. Res. 2022 10 4 39576 10.52965/001c.39576 36425231
    [Google Scholar]
  59. Dawson T.M. Dawson V.L. Nitric oxide synthase: Role as a transmitter/mediator in the brain and endocrine system. Annu. Rev. Med. 1996 47 219 227 10.1146/annurev.med.47.1.219 8712777
    [Google Scholar]
  60. Wegener G. Volke V. Nitric oxide synthase inhibitors as antidepressants. Pharmaceuticals (Basel) 2010 3 1 273 299 10.3390/ph3010273 27713253
    [Google Scholar]
  61. Pourhamzeh M. Moravej F.G. Arabi M. Shahriari E. Mehrabi S. Ward R. Ahadi R. Joghataei M.T. The roles of serotonin in neuropsychiatric disorders. Cell. Mol. Neurobiol. 2022 42 6 1671 1692 10.1007/s10571‑021‑01064‑9 33651238
    [Google Scholar]
  62. Celada P. Bortolozzi A. Artigas F. Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: Rationale and current status of research. CNS Drugs 2013 27 9 703 716 10.1007/s40263‑013‑0071‑0 23757185
    [Google Scholar]
  63. Simpson E.H. Gallo E.F. Balsam P.D. Javitch J.A. Kellendonk C. How changes in dopamine D2 receptor levels alter striatal circuit function and motivation. Mol. Psychiatry 2022 27 1 436 444 10.1038/s41380‑021‑01253‑4 34385603
    [Google Scholar]
  64. Li X. Teng T. Yan W. Fan L. Liu X. Clarke G. Zhu D. Jiang Y. Xiang Y. Yu Y. Zhang Y. Yin B. Lu L. Zhou X. Xie P. AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models. Transl. Psychiatry 2023 13 1 200 10.1038/s41398‑023‑02486‑3 37308476
    [Google Scholar]
  65. Zhang R. Yang Y. Dong W. Lin M. He J. Zhang X. Tian T. Yang Y. Chen K. Lei Q.Y. Zhang S. Xu Y. Lv L. D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1. Proc. Natl. Acad. Sci. USA 2022 119 8 e2114851119 10.1073/pnas.2114851119 35181605
    [Google Scholar]
  66. Chen Y. Guan W. Wang M.L. Lin X.Y. PI3K-AKT/mTOR signaling in psychiatric disorders: A valuable target to stimulate or suppress? Int. J. Neuropsychopharmacol. 2024 27 2 pyae010 10.1093/ijnp/pyae010 38365306
    [Google Scholar]
  67. Chen Z.R. Huang J.B. Yang S.L. Hong F.F. Role of cholinergic signaling in alzheimer’s disease. Molecules 2022 27 6 1816 10.3390/molecules27061816 35335180
    [Google Scholar]
  68. Sultzer D.L. Lim A.C. Gordon H.L. Yarns B.C. Melrose R.J. Cholinergic receptor binding in unimpaired older adults, mild cognitive impairment, and Alzheimer’s disease dementia. Alzheimers Res. Ther. 2022 14 1 25 10.1186/s13195‑021‑00954‑w 35130968
    [Google Scholar]
  69. Hessel S.S. Dwivany F.M. Zainuddin I.M. Wikantika K. Celik I. Emran T.B. Tallei T.E. A computational simulation appraisal of banana lectin as a potential anti-SARS-CoV-2 candidate by targeting the receptor-binding domain. J. Genet. Eng. Biotechnol. 2023 21 1 148 10.1186/s43141‑023‑00569‑8 38015308
    [Google Scholar]
  70. Rudrapal M. Celik I. Khan J. Ansari M.A. Alomary M.N. Alatawi F.A. Yadav R. Sharma T. Tallei T.E. Pasala P.K. Sahoo R.K. Khairnar S.J. Bendale A.R. Zothantluanga J.H. Chetia D. Walode S.G. Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations. J. King Saud Univ. Sci. 2022 34 3 101826 10.1016/j.jksus.2022.101826 35035181
    [Google Scholar]
  71. Džoljić E. Grbatinić I. Kostić V. Why is nitric oxide important for our brain? Funct. Neurol. 2015 30 3 159 163 10.11138/FNeur/2015.30.3.159 26910176
    [Google Scholar]
  72. Chen K. Pittman R.N. Popel A.S. Nitric oxide in the vasculature: Where does it come from and where does it go? A quantitative perspective. Antioxid. Redox Signal. 2008 10 7 1185 1198 10.1089/ars.2007.1959 18331202
    [Google Scholar]
  73. Tripathi P. Nitric oxide and immune response. Indian J. Biochem. Biophys. 2007 44 5 310 319 18341206
    [Google Scholar]
  74. Ghasemi M. Claunch J. Niu K. Pathologic role of nitrergic neurotransmission in mood disorders. Prog. Neurobiol. 2019 173 54 87 10.1016/j.pneurobio.2018.06.002 29890213
    [Google Scholar]
  75. Pennanen L. van der Hart M. Yu L. Tecott L.H. Impact of serotonin (5-HT)2C receptors on executive control processes. Neuropsychopharmacology 2013 38 6 957 967 10.1038/npp.2012.258 23303047
    [Google Scholar]
  76. Matsumoto K. Mizowaki M. Takayama H. Sakai S.I. Aimi N. Watanabe H. Suppressive effect of mitragynine on the 5-methoxy-N,N-dimethyltryptamine-induced head-twitch response in mice. Pharmacol. Biochem. Behav. 1997 57 1-2 319 323 10.1016/S0091‑3057(96)00314‑0 9164589
    [Google Scholar]
  77. Zhang G. Stackman R.W. The role of serotonin 5-HT2A receptors in memory and cognition. Front. Pharmacol. 2015 6 225 10.3389/fphar.2015.00225 26500553
    [Google Scholar]
  78. Hoyer D. 5-HT-2C Receptor. xPharm: The Comprehensive Pharmacology Enna S.J. Bylund D.B.B.T.T.C.P.R. New York Elsevier 2007 1 11
    [Google Scholar]
  79. Nakao K. Singh M. Sapkota K. Fitzgerald A. Hablitz J.J. Nakazawa K. 5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction. Transl. Psychiatry 2022 12 1 168 10.1038/s41398‑022‑01930‑0 35459266
    [Google Scholar]
  80. Kim S.A. 5-HT1A and 5-HT2A signaling, desensitization, and downregulation: Serotonergic dysfunction and abnormal receptor density in schizophrenia and the prodrome. Cureus 2021 13 6 e15811 10.7759/cureus.15811 34306878
    [Google Scholar]
  81. García-Bea A. Miranda-Azpiazu P. Muguruza C. Marmolejo-Martinez-Artesero S. Diez-Alarcia R. Gabilondo A.M. Callado L.F. Morentin B. González-Maeso J. Meana J.J. Serotonin 5-HT2A receptor expression and functionality in postmortem frontal cortex of subjects with schizophrenia: Selective biased agonism via Gαi1-proteins. Eur. Neuropsychopharmacol. 2019 29 12 1453 1463 10.1016/j.euroneuro.2019.10.013 31734018
    [Google Scholar]
  82. Akil M. Kolachana B.S. Rothmond D.A. Hyde T.M. Weinberger D.R. Kleinman J.E. Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J. Neurosci. 2003 23 6 2008 2013 10.1523/JNEUROSCI.23‑06‑02008.2003 12657658
    [Google Scholar]
  83. Murugan N.A. Muvva C. Jeyarajpandian C. Jeyakanthan J. Subramanian V. Performance of force-field- and machine learning-based scoring functions in ranking MAO-B protein–inhibitor complexes in relevance to developing parkinson’s therapeutics. Int. J. Mol. Sci. 2020 21 20 7648 10.3390/ijms21207648 33081086
    [Google Scholar]
/content/journals/cpd/10.2174/0113816128335217241031033104
Loading
Probing the Molecular Mechanisms of Kratom's Antipsychotic Effects through a Multi-modal Computational Approach
Bentham Science Publishers ; https://doi.org/10.2174/0113816128335217241031033104
/content/journals/cpd/10.2174/0113816128335217241031033104
/content/journals/cpd/10.2174/0113816128335217241031033104
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keywords: antipsychotic ; herbal remedies ; molecular mechanism ; Kratom ; mitragynine ; network pharmacology

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test