Therapeutical Potential of 5-HT6 of Receptor Modulation in Neurological and Psychiatric Conditions


Authors : Tuolor.Rosy; Dil Prasad Subba; Debba.Farah

Volume/Issue : Volume 9 - 2024, Issue 5 - May

Google Scholar : https://tinyurl.com/43hsuazf

Scribd : https://tinyurl.com/3fsfw5u8

DOI : https://doi.org/10.38124/ijisrt/IJISRT24MAY1325

Abstract : This review examines the pharmacological effects of targeting 5-HT6 receptors, a subtype of serotonin receptors found primarily in the hippocampus. These receptors are essential for synaptic function, functional plasticity and various cognitive functions such as learning and memory. The review synthesizes the existing literature to investigate the potential therapeutic use of drugs targeting 5-HT6 receptors in neurological and psychiatric conditions, including Alzheimer's disease, schizophrenia, depression, anxiety, neurodegenerative diseases and pregnancy mood disorders. Although some preclinical studies suggest positive precognitive effects, these results have often conflicted with clinical research; therefore more work needs to be done on drug classification and therapeutic effect as well as dosage considerations.

Keywords : 5-HT6 Receptors, Serotonin, Pharmacology, Cognitive Function, Neurological Statics. , Psychiatric Disorders.

References :

  1. Caroline, Lahogue., Jean-Marie, Billard., Thomas, Freret., Valentine, Bouet. (2023). 5-HT6 Receptors Sex-Dependently Modulate Hippocampal Synaptic Activity through GABA Inhibition. Biomolecules,  Available from: 10.3390/biom13050751.
  2. Séverine, Chaumont-Dubel., Sonya, Galant., Matthieu, Prieur., Tristan, Bouschet., Joël, Bockaert., Philippe, Marin. (2023). Impact of 5-HT6 Receptor Subcellular Localization on Its Signaling and Its Pathophysiological Roles. Cells,  Available from: 10.3390/cells12030426.
  3. Ramakrishna, Nirogi., Pradeep, Jayarajan., Anil, Shinde., Abdul, Rasheed, Mohammed., Venkata, Ramalingayya, Grandhi., Vijay, Benade., Vinod, Kumar, Goyal., Renny, Abraham., Venkateswarlu, Jasti., Jeffrey, L., Cummings. (2023). Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders. Biomolecules, Available from: 10.3390/biom13020309.
  4. Tsvetkova,, Milena,,. (2023). Serotonin receptors.   Available from: 10.1016/b978-0-323-85492-4.00050-8.
  5. Santiago, Ballaz., Michel, Bourin. (2023). Anti-Inflammatory Therapy as a Promising Target in Neuropsychiatric Disorders. Advances in Experimental Medicine and Biology,  Available from: 10.1007/978-981-19-7376-5_20.
  6. Michele, Tufano., Graziano, Pinna. (2020). Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders? Molecules,  Available from: 10.3390/MOLECULES25051062.
  7. Tanya, L., Wallace., Theresa, M., Ballard., Bruno, Pouzet., Wim, J., Riedel., Joseph, G., Wettstein. (2011). Drug targets for cognitive enhancement in neuropsychiatric disorders. Pharmacology, Biochemistry and Behavior,  Available from: 10.1016/J.PBB.2011.03.022
  8. Dietrich, van, Calker., Knut, Biber., Katharina, Domschke., Tsvetan, Serchov. (2019). The role of adenosine receptors in mood and anxiety disorders. Journal of Neurochemistry,  Available from: 10.1111/JNC.14841.
  9. Janak, R., Awasthi., Janak, R., Awasthi., Kota, Tamada., Eric, T., N., Overton., Toru, Takumi., Toru, Takumi., Toru, Takumi. (2021). Comprehensive topographical map of the serotonergic fibres in the male mouse brain. The Journal of Comparative Neurology,  Available from: 10.1002/CNE.25027.
  10. Gunnar, Flik., Joost, H.A., Folgering., Thomas, I., H., F., Cremers., Ben, H.C., Westerink., Eliyahu, Dremencov. (2015). Interaction Between Brain Histamine and Serotonin, Norepinephrine, and Dopamine Systems: In Vivo Microdialysis and Electrophysiology Study. Journal of Molecular Neuroscience,  Available from: 10.1007/S12031-015-0536-3.
  11. Anu, Kinnunen., Minnamaija, Lintunen., Kaj, Karlstedt., Hiroyuki, Fukui., Pertti, Panula., Pertti, Panula. (1998). In situ detection of H1‐receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain. The Journal of Comparative Neurology,  Available from: 10.1002/(SICI)1096-9861(19980427)394:1<127::AID-CNE10>3.0.CO;2-L.
  12. Ramírez MJ. 5-HT6 receptors and Alzheimer's disease. Alzheimers Res Ther. 2013 Apr 22;5(2):15. doi: 10.1186/alzrt169. PMID: 23607787; PMCID: PMC3706851.
  13. Zehui, Sun., Bingjie, Wang., Chen, Chen., Chenjian, Li., Zhang, Yan., Zhang, Yan. (2021). 5-HT6R null mutation induces synaptic and cognitive defects. Aging Cell,  Available from: 10.1111/ACEL.13369.
  14. Ramakrishna, Nirogi., Pradeep, Jayarajan., Anil, Shinde., Abdul, Rasheed, Mohammed., Venkata, Ramalingayya, Grandhi., Vijay, Benade., Vinod, Kumar, Goyal., Renny, Abraham., Venkateswarlu, Jasti., Jeffrey, L., Cummings. (2023). Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders. Biomolecules,  Available from: 10.3390/biom13020309.
  15. Ramakrishna, Nirogi., Pradeep, Jayarajan., Anil, Shinde., Abdul, Rasheed, Mohammed., Venkata, Ramalingayya, Grandhi., Vijay, Benade., Vinod, Kumar, Goyal., Renny, Abraham., Venkateswarlu, Jasti., Jeffrey, L., Cummings. (2023). Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders. Biomolecules,  Available from: 10.3390/biom13020309.
  16. Jiayi, Li. (2023). Role of 5-HT receptors and transporters in psychiatric disorders.   Available from: 10.1117/12.2668997.
  17. Etsay, Weldekidan, Tsegay., Desalegn, Getnet, Demise., Nigus, Alemu, Hailu., Zenawi, Hagos, Gufue. (2020). Serotonin Type 6 and 7 Receptors as a Novel Therapeutic Target for the Treatment of Schizophrenia. Neuropsychiatric Disease and Treatment,  Available from: 10.2147/NDT.S263424.
  18. Anand, M., Bokare., A., K., Praveenkumar., Mandar, Bhonde., Yogendra, Nayak., Ravindra, Pal., Rajan, Goel. (2017). 5-HT6 Receptor Agonist and Antagonist Against β-Amyloid-Peptide-Induced Neurotoxicity in PC-12 Cells. Neurochemical Research,  Available from: 10.1007/S11064-017-2217-9.
  19. Ahmed, Nawaz, Ahmed. (2015). Investigating the neuroprotective potential of short-term 5-HT7 receptor activation against neuronal excitotoxicity.
  20. Krzysztof, Więckowski., Natalia, Szałaj., Beata, Gryzło., Tomasz, Wichur., Izabella, Góral., Emilia, Sługocka., Joanna, Śniecikowska., Gniewomir, Latacz., Agata, Siwek., Justyna, Godyń., Adam, Bucki., Marcin, Kołaczkowski., Anna, Wieckowska. (2022). Serotonin 5-HT6 Receptor Ligands and Butyrylcholinesterase Inhibitors Displaying Antioxidant Activity—Design, Synthesis and Biological Evaluation of Multifunctional Agents against Alzheimer’s Disease. International Journal of Molecular Sciences,  Available from: 10.3390/ijms23169443.
  21. Delphine, Karila., Thomas, Freret., Valentine, Bouet., Michel, Boulouard., Patrick, Dallemagne., Christophe, Rochais. (2015). Therapeutic Potential of 5-HT6 Receptor Agonists. Journal of Medicinal Chemistry,  Available from: 10.1021/ACS.JMEDCHEM.5B00179.
  22. Michèle, Sebben., Hervé, Ansanay., Joël, Bockaert., Aline, Dumuis. (1994). 5-HT6 receptors positively coupled to adenylyl cyclase in striatal neurones in culture. Neuroreport,  Available from: 10.1097/00001756-199412000-00037.
  23. 23.Amanda, Alves, Marcelino, da, Silva., Mayara, Matias, Oliveira., Taisy, Cinthia, Ferro, Cavalcante., Larissa, Cavalcanti, do, Amaral, Almeida., Paula, Luiza, Menezes, Cruz., Sandra, Lopes, de, Souza. (2018). Undernutrition during pregnancy and lactation increases the number of fos-cells in the reward system in response to a 5-HT6 receptor agonist in male adolescent rats. International Journal of Food Sciences and Nutrition,  Available from: 10.1080/09637486.2017.1382455.
  24. Jimena, Laporta., Tonia, L., Peters., Kathryn, E., Merriman., Chad, M., Vezina., Laura, L., Hernandez. (2013). Serotonin (5-HT) Affects Expression of Liver Metabolic Enzymes and Mammary Gland Glucose Transporters during the Transition from Pregnancy to Lactation. PLOS ONE,  Available from: 10.1371/JOURNAL.PONE.0057847.
  25. Nicholas, J., Jury., Betsy, A., McCormick., Nelson, D., Horseman., Stephen, C., Benoit., 26.Karen, A., Gregerson. (2015). Enhanced responsiveness to selective serotonin reuptake inhibitors during lactation. PLOS ONE,  Available from: 10.1371/JOURNAL.PONE.0117339.
  26. Laura, Pogliani., Sara, Baldelli., Dario, Cattaneo., P., Pileri., Emilio, Clementi., Irene, Cetin., Gian, Vincenzo, Zuccotti. (2019). Selective serotonin reuptake inhibitors’ passage into human milk of lactating women. Journal of Maternal-fetal & Neonatal Medicine,  Available from: 10.1080/14767058.2018.1455180.
  27. 28.Schechter, L. E., Lin, Q., Smith, D. L., Zhang, G., Shan, Q., Platt, B., Brandt, M. R., Dawson, L. A., Cole, D., Bernotas, R., Robichaud, A., Rosenzweig-Lipson, S., & Beyer, C. E. (2008). Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466. Neuropsychopharmacology: official publication of the American College of 2.Neuropsychopharmacology33(6), 1323–1335. https://doi.org/10.1038/sj.npp.1301503.
  28. 29.West PJ, Marcy VR, Marino MJ, Schaffhauser H (December 2009). "Activation of the 5-HT(6) receptor attenuates long-term potentiation and facilitates GABAergic neurotransmission in rat hippocampus". Neuroscience164 (2): 692–701. doi:10:101016/j neuroscience .2009.
  29. Carr GV, Schechter LE, Lucki I. Antidepressant and anxiolytic effects of selective 5-HT6 receptor agonists in rats. Psychopharmacology (Berl). 2011 Feb;213(2-3):499-507. doi: 10.1007/s00213-010-1798-7. Epub 2010 Mar 9. PMID: 20217056; PMCID: PMC2910165.
  30. 31.Wesołowska A, Rychtyk J, Gdula-Argasińska J, et al. Effect of 5-HT6 Receptor Ligands Combined with Haloperidol or Risperidone on Antidepressant-/Anxiolytic-Like Behavior and BDNF Regulation in Hippocampus and Prefrontal Cortex of Rats. Neuropsychiatr Dis Treat. 2021;17:2105-2127. Published 2021 Jun 25. doi:10.2147/NDT.S309818.
  31. Woods S, Clarke NN, Layfield R, Fone KC. 5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. Br J Pharmacol. 2012 Sep;167(2):436-49. doi: 10.1111/j.1476-5381.2012.02022.x. PMID: 22568655.
  32. Andrews M, Tousi B, Sabbagh MN. 5HT6 Antagonists in the Treatment of Alzheimer's Dementia: Current Progress. Neurol Ther. 2018 Jun;7(1):51-58. doi: 10.1007/s40120-018-0095.
  33. Woods S, Clarke NN, Layfield R, Fone KC. 5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. Br J Pharmacol. 2012 Sep;167(2):436-49. doi: 10.1111/j.1476-5381.2012.02022.x. PMID: 22568655; PMCID: PMC3481049.
  34. Dalal PK, Kar SK, Agarwal SK. Management of Psychiatric Disorders in Patients with Chronic Kidney Diseases. Indian J Psychiatry. 2022 Mar;64(Suppl 2): S394-S401. doi: 36.4103/indianjpsychiatry.indianjpsychiatry_1016_21. Epub 2022 Mar 23. PMID: 35602366; PMCID: PMC9122172.
  35. Woods S, Clarke NN, Layfield R, Fone KC. 5-HT(6) receptor agonists and antagonists enhance learning and memory in a conditioned emotion response paradigm by modulation of cholinergic and glutamatergic mechanisms. Br J Pharmacol. 2012 Sep;167(2):436-49. doi: 10.1111/j.1476-5381.2012.02022.x. PMID: 22568655; PMCID: PMC3481049.
  36. Ayeni EA, Aldossary AM, Ayejoto DA, Gbadegesin LA, Alshehri AA, Alfassam HA, Afewerky HK, Almughem FA, Bello SM, Tawfik EA. Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities. Int J Environ Res Public Health. 2022 Sep 30;19(19):12495. doi: 10.3390/ijerph191912495. PMID: 36231792; PMCID: PMC9564880.
  37. Fisas, Angels (August 2006). "Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats". British Journal of Pharmacology. doi:10.1038/sj.bjp.0706807. PMC 1751931.
  38. Garfield, A. S.; Heisler, L. K. (24 November 2008). "Pharmacological targeting of the serotonergic system for the treatment of obesity"The Journal of Physiologydoi:10.1113/jphysiol.2008.164152
  39. Rongzhe, Guo., Yaohua, Hou. (2010). E-easy series connector assembly with shielding function.  
  40. Vimla, Band., Qingshen, Gao. (1999). E6 targeted protein (E6TP1).   
  41. Chen, Yihua. (2019). Action mechanism used for object detection and object detection device.  
  42. Huang, Donglin., Xia, Xiaomin., Si, Yingge. (2017). Action mechanism of the residual current operated circuit breaker. 
  43. Komine, Motohiro. (2020). Action mechanism for keyboard instrument.  
  44. Wade, James, Eugene., Kanakapura, Venugopalan, Navaneethan., Corujo, Rigoberto., Schunicht, Geoffery. (2021). Event action management mechanism.   
  45. Ian, Kendall., Helge, A., Slotten., Xavier, Codony., Javier, Burgueño., Peter, J., Pauwels., José, Miguel, Vela., Kevin, C., F., Fone. (2011). E-6801, a 5-HT 6 receptor agonist, improves recognition memory by combined modulation of cholinergic.  
  46. Guilherme, Silva, Fracarolli. (2021). Mapping Online Geographical Indication: Agrifood Products on E-Commerce Shelves of Mercosur and the European Union. Economies,  Available from: 10.3390/ECONOMIES9020084.
  47. Guilherme, Silva, Fracarolli. (2021). Mapping Online Geographical Indication: Agri-Food Markets on E-Retail Shelves. Agronomy,  Available from: 10.3390/AGRONOMY11122385.
  48. C., Chung., A., Dimitrios, Colevas., Douglas, Adkins., Jong, Chul, Park., Cristina, Rodríguez., Michael, K., Gibson., Ammar, Sukari., Barbara, Burtness., Faye, M., Johnson., Ricklie, Julian., Nabil, F., Saba., Lara, Dunn., Tanguy, Y., Seiwert., Francis, P., Worden., Rami, Y., Haddad., Nashat, Y., Gabriel., Julie, E., Bauman., Laura, Agensky., Apollina, Goel., Reena, Lynam., Steven, P., Margossian., Raymond, J., Moniz., Steven, N., Quayle., Cynthia, Rajan., Kenneth, J., Pienta., Matteo, G., Levisetti., Sara, I., Pai. (2022). 681 A phase 1 study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer.   Available from: 10.1136/jitc-2022-sitc2022.0681.
  49. Da-Yi, Peng. (2011). Indication device and manufacturing method thereof and electronic device provided with same.  
  50. Du, Zhuo., Pan, Yu., Kuang, Cuiqiong., Wen, Haizhen. (2018). Electronic indication pen.  
  51. Mellner, Thomas., Schneider, Hans-Peter, Dipl-Ing. (1993). Device for creation and control of indication signals.  
  52. Yasuhide, Suzuki., Shuzo, Seo., Shinichi, Kakiuchi. (2005). Indication-selecting device for an electronic device and an indication-selecting method.  
  53. Li, Wei., Wang, Shoucheng., Yu, Binke. (2019). Method and electronic device for displaying indication information.  
  54. S., Msika., M., Coupaye. (2008). Les Contre-Indications de la Chirurgie Bariatrique.  
  55. Ana, Beatriz, Leite, Bueno., André, José, Galadinovic, Bachiega., Lyvia, Rodrigues, Parreira, Braga., Renata, Santos, Borges., Aline, Macedo, La, Ruina, Doering., Ana, Cecília, FERREIRA, MONTEIRO., Camila, Lopes, de, Oliveira., Raquel, Rocha, Machado. (2022). Contraindicações aos métodos contraceptivos combinados. Revista Saúde Multidisciplinar,  Available from: 10.53740/rsm.v12i2.432.
  56. J., Teitelbaum., P., Bouletreau., P., Breton., Freidel, M. (2007). [Is condylar resorption a contra-indication for surgery?]. Revue De Stomatologie Et De Chirurgie Maxillo-faciale,  Available from: 10.1016/J.STOMAX.2007.01.004.
  57. Elie, Mousseaux. (1999). Les contre-indications à l’IRM. Sang Thrombose Vaisseaux, 
  58. Ian, Kendall., Helge, A., Slotten., Xavier, Codony., Javier, Burgueño., Peter, J., Pauwels., José, Miguel, Vela., Kevin, C., F., Fone. (2011). E-6801, a 5-HT 6 receptor agonist, improves recognition memory by combined modulation of cholinergic.  
  59. Ian, Kendall., Helge, A., Slotten., Xavier, Codony., Javier, Burgueño., Peter, J., Pauwels., José, Miguel, Vela., Kevin, C., F., Fone. (2011). E-6801, a 5-HT6 receptor agonist, improves recognition memory by combined modulation of cholinergic and glutamatergic neurotransmission in the rat. Psychopharmacology,  Available from: 10.1007/S00213-010-1854-3.
  60. Warren, Robinson., Chandrika, Carr. (2014). E-Z Dose-Pensing. 
  61. C., Chung., A., Dimitrios, Colevas., Douglas, Adkins., Jong, Chul, Park., Cristina, Rodríguez., Michael, K., Gibson., Ammar, Sukari., Barbara, Burtness., Faye, M., Johnson., Ricklie, Julian., Nabil, F., Saba., Lara, Dunn., Tanguy, Y., Seiwert., Francis, P., Worden., Rami, Y., Haddad., Nashat, Y., Gabriel., Julie, E., Bauman., Laura, Agensky., Apollina, Goel., Reena, Lynam., Steven, P., Margossian., Raymond, J., Moniz., Steven, N., Quayle., Cynthia, Rajan., Kenneth, J., Pienta., Matteo, G., Levisetti., Sara, I., Pai. (2022). 681 A phase 1 study of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck cancer.   Available from: 10.1136/jitc-2022-sitc2022.0681.
  62. Ian, Kendall., Helge, A., Slotten., Xavier, Codony., Javier, Burgueño., Peter, J., Pauwels., José, Miguel, Vela., Kevin, C., F., Fone. (2011). E-6801, a 5-HT 6 receptor agonist, improves recognition memory by combined modulation of cholinergic.  
  63. Michael, Pokrass., Peter, Rosenthal., Joshua, E., Messinger., Jessica, Field., Heba, Nowyhed. (2023). Abstract 681: ICVB-1042, an oncolytic adenovirus, infects and kills bladder, breast, and glioblastoma human dissociated tumour cells. Cancer Research,  Available from: 10.1158/1538-7445.am2023-681.
  64. Agnieszka, Nikiforuk., Tomasz, Kos., Anna, Wesołowska. (2011). The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration. Psychopharmacology,  Available from: 10.1007/S00213-011-2297-1.
  65. S., S, S., Ranjit., S., E., Loo., S., Zulkifli. (2011). EMD: Electricity Monitoring Device for User Awareness.   Available from: 10.1109/ISMS.2011.33.
  66. Magdalena, Kotańska., Joanna, Śniecikowska., Magdalena, Jastrzębska-Więsek., Marcin, Kołaczkowski., Karolina, Pytka. (2017). Metabolic and Cardiovascular Benefits and Risks of EMD386088-A 5-HT6 Receptor Partial Agonist and Dopamine Transporter Inhibitor. Frontiers in Neuroscience,  Available from: 10.3389/FNINS.2017.00050
  67. Craig, Bettenhausen. (2023). EMD to expand electronic gases.   Available from: 10.1021/cen-10113-buscon12.
  68. Agnieszka, Nikiforuk., Tomasz, Kos., Anna, Wesołowska. (2011). The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration. Psychopharmacology,  Available from: 10.1007/S00213-011-2297-1.
  69. Jonas, Zalinkevicius., Rita, Butkiene. (2019). Automatic detection of contraindications of medicines in package leaflets.
  70. Analgesics in Pregnancy and Lactation: Safe Medication Practices..  (2023).
  71. Mark, Donaldson., Jason, H, Goodchild. (2023). Analgesics in Pregnancy and Lactation: Safe Medication Practices.  
  72. Manoj, K., Sahoo., Harshita, Biswas., Sandeep, Grover. (2023). Safety Profile of Aripiprazole During Pregnancy and Lactation: Report of 2 Cases. Turkish Journal of Psychiatry,  Available from: 10.5080/u26681.
  73. Craig, Bettenhausen. (2023). EMD to expand electronic gases.   Available from: 10.1021/cen-10113-buscon12.
  74. Agnieszka, Nikiforuk., Tomasz, Kos., Anna, Wesołowska. (2011). The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration. Psychopharmacology,  Available from: 10.1007/S00213-011-2297-1.
  75. Jingyuan, Feng., Chunyong, Yang. (2019). EMD-Based Noise Suppression Technology for Indoor Visible Light Communication System.   Available from: 10.1109/OGC.2019.8925279.
  76. Magdalena, Jastrzębska-Więsek., Agata, Siwek., Anna, Partyka., Lucyna, Antkiewicz-Michaluk., Jerzy, Michaluk., Irena, Romańska., Marcin, Kołaczkowski., Anna, Wesołowska. (2016). Study of a mechanism responsible for potential antidepressant activity of EMD 386088, a 5-HT6 partial agonist in rats.. Naunyn-schmiedebergs Archives of Pharmacology,  Available from: 10.1007/S00210-016-1245-3.
  77. Magdalena, Jastrzębska-Więsek., Agata, Siwek., Anna, Partyka., Bernadeta, Szewczyk., Magdalena, Sowa-Kućma., Anna, Wasik., Marcin, Kołaczkowski., Anna, Wesołowska. (2015). Antidepressant-like activity of EMD 386088, a 5-HT6 receptor partial agonist, following systemic acute and chronic administration to rats. Naunyn-schmiedebergs Archives of Pharmacology,  Available from: 10.1007/S00210-015-1141-2.
  78. Agnieszka, Nikiforuk., Katarzyna, Fijał., Agnieszka, Potasiewicz., Piotr, Popik., Tomasz, Kos. (2013). The 5-hydroxytryptamine (serotonin) receptor 6 agonists EMD 386088 ameliorates ketamine-induced deficits in attentional set-shifting and novel object recognition, but not in the prepulse inhibition in rats. Journal of Psychopharmacology,  Available from: 10.1177/0269881113480991.
  79. Agnieszka, Nikiforuk., Tomasz, Kos., Anna, Wesołowska. (2011). The 5-HT6 receptor agonist EMD 386088 produces antidepressant and anxiolytic effects in rats after intrahippocampal administration. Psychopharmacology,  Available from: 10.1007/S00213-011-2297-1.
  80. Frank, G., Boess., Frederick, J., Monsma., Sleight, Andrew. (2002). Identification of residues in transmembrane regions III and VI that contribute to the ligand binding site of the serotonin 5-HT6 receptor. Journal of Neurochemistry,  Available from: 10.1046/J.1471-4159.1998.71052169.X.
  81. Sleight, Andrew., Frank, G., Boess., Michael, Bös., Bernard, Levet-Trafit., Claus, Riemer., Anne, Bourson. (1998). Characterization of Ro 04-6790 and Ro 63-0563: potent and selective antagonists at human and rat 5-HT6 receptors. British Journal of Pharmacology,  Available from: 10.1038/SJ.BJP.0701851.
  82. Charles, Alan, Reavill., Carol, Routledge. (1999). Use of 5ht-6 antagonists for the treatment of ADHD.
  83. James, L., Bennett., George, K., Aghajanian. (2011). Response of single raphé neurons to (+)-LSD: correlation with (+)-LSD binding in the brain. Journal of Pharmacy and Pharmacology,  Available from: 10.1111/J.2042-7158.1976.TB02779.X.
  84. James, L., Bennett., George, K., Aghajanian. (2011). Response of single raphé neurons to (+)-LSD: correlation with (+)-LSD binding in the brain. Journal of Pharmacy and Pharmacology,  Available from: 10.1111/J.2042-7158.1976.TB02779.X.
  85. Julia, T., Brouard., Judith, Schweimer., Rachel, Houlton., Katherine, E., Burnham., Philip, Quérée., Trevor, Sharp. (2015). Pharmacological Evidence for 5-HT6 Receptor Modulation of 5-HT Neuron Firing in Vivo. ACS Chemical Neuroscience,  Available from: 10.1021/ACSCHEMNEURO.5B00061.
  86. Nils-Erik, Andén., Hans, Corrodi., Kjell, Fuxe., Tomas, Hökfelt. (1968). Evidence for a central 5-hydroxytryptamine receptor stimulation by lysergic acid diethylamide. British Journal of Pharmacology,  Available from: 10.1111/J.1476-5381.1968.TB07943.X.
  87. Alfredo, Meneses., Georgina, Perez-Garcia., Teresa, Ponce-Lopez., C., Castillo. (2011). 5-HT6 receptor memory and amnesia: behavioural pharmacology--learning and memory processes. International Review of Neurobiology,  Available from: 10.1016/B978-0-12-385902-0.00002-4.
  88. (2023). Lysergic acid diethylamide stimulates cardiac human H2 histamine receptors.   Available from: 10.21203/rs.3.rs-2898645/v1.
  89. Anne, Bourson., E., Borroni., R.H., Austin., Frederick, J., Monsma., Sleight, Andrew. (1995). Determination of the role of the 5-ht6 receptor in the rat brain: a study using antisense oligonucleotides. Journal of Pharmacology and Experimental Therapeutics,
  90. María, L., López-Rodríguez., Bellinda, Benhamú., Tania, de, la, Fuente., Arantxa, Sanz., Leonardo, Pardo., Mercedes, Campillo. (2005). A Three-Dimensional Pharmacophore Model for 5-Hydroxytryptamine6 (5-HT6) Receptor Antagonists. Journal of Medicinal Chemistry,  Available from: 10.1021/JM050247C.
  91. Maddaford, Shawn., Tao, Xin., Abdelmalik, Slassi., Ashok, Tehim., Qiao, Qi. (1999). Bicyclic piperidine and piperazine compounds have 5-ht6 receptor affinity.  
  92. 94. Alexandre, Vasilievich, Ivachtchenko., E., S., Golovina., Madina, G., Kadieva., Oleg, D., Mitkin., Ilya, Okun. (2013). 5-Ht6 Receptor Antagonists. V. Structure-Activity Relationship of (4-Phenylsulfonyloxazol-5-yl)amines. Pharmaceutical Chemistry Journal,  Available from: 10.1007/S11094-013-0861-1.
  93. James, R., Hauske. (2006). Multimediator 5-ht6 receptor antagonists, and uses related thereto.  
  94. Ramakrishna, Nirogi., Pradeep, Jayarajan., Anil, Shinde., Abdul, Rasheed, Mohammed., Venkata, Ramalingayya, Grandhi., Vijay, Benade., Vinod, Kumar, Goyal., Renny, Abraham., Venkateswarlu, Jasti., Jeffrey, L., Cummings. (2023). Progress in Investigational Agents Targeting Serotonin-6 Receptors for the Treatment of Brain Disorders. Biomolecules,  Available from: 10.3390/biom13020309.
  95. Donatella, Marazziti., Stefano, Baroni., Franco, Borsini., M., Picchetti., Elena, Vatteroni., Valentina, Falaschi., Mario, Catena-Dell'Osso. (2013). Serotonin Receptors of Type 6 (5-HT6): From Neuroscience to Clinical Pharmacology. Current Medicinal Chemistry,  Available from: 10.2174/0929867311320030008.
  96. (2023). Lysergic acid diethylamide: In search of the wonder drug.   Available from: 10.1093/med/9780192863607.003.0005.
  97. Ellen, Siobhan, Mitchell. (2011). 5-HT6 receptor ligands as anti-dementia drugs. International Review of Neurobiology,  Available from: 10.1016/B978-0-12-385902-0.00007-3.
  98. Julia, T., Brouard., Judith, Schweimer., Rachel, Houlton., Katherine, E., Burnham., Philip, Quérée., Trevor, Sharp. (2015). Pharmacological Evidence for 5-HT6 Receptor Modulation of 5-HT Neuron Firing in Vivo. ACS Chemical Neuroscience,  Available from: 10.1021/ACSCHEMNEURO.5B00061.
  99. Ramakrishna, Nirogi., Koteshwara, Mudigonda., Gopinadh, Bhyrapuneni., Nageswara, Rao, Muddana., Vinod, Kumar, Goyal., Santosh, Kumar, Pandey., Raghava, Choudary, Palacharla. (2018). Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects. Clinical Drug Investigation,  Available from: 10.1007/S40261-018-0618-4.
  100. Ramírez, M.J. 5-HT6 receptors and Alzheimer's disease. Alz Res Therapy 5, 15 (2013). https://doi.org/10.1186/alzrt169.

This review examines the pharmacological effects of targeting 5-HT6 receptors, a subtype of serotonin receptors found primarily in the hippocampus. These receptors are essential for synaptic function, functional plasticity and various cognitive functions such as learning and memory. The review synthesizes the existing literature to investigate the potential therapeutic use of drugs targeting 5-HT6 receptors in neurological and psychiatric conditions, including Alzheimer's disease, schizophrenia, depression, anxiety, neurodegenerative diseases and pregnancy mood disorders. Although some preclinical studies suggest positive precognitive effects, these results have often conflicted with clinical research; therefore more work needs to be done on drug classification and therapeutic effect as well as dosage considerations.

Keywords : 5-HT6 Receptors, Serotonin, Pharmacology, Cognitive Function, Neurological Statics. , Psychiatric Disorders.

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