5-HT6 Receptor - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

5-HT6 Receptor

The Experts below are selected from a list of 45939 Experts worldwide ranked by ideXlab platform

Alexandre V. Ivachtchenko – One of the best experts on this subject based on the ideXlab platform.

  • 5-HT6 Receptor Antagonists. V. Structure – Activity Relationship of (4-Phenylsulfonyloxazol-5-yl)amines
    Pharmaceutical Chemistry Journal, 2013
    Co-Authors: Alexandre V. Ivachtchenko, E. S. Golovina, Madina G. Kadieva, Oleg D. Mitkin, Ilya Okun

    Abstract:

    Both novel and previously reported (4-phenylsulfonyloxazol-5-yl)amine derivatives containing a substituted sulfonyl group were studied in order to discover highly active 5-HT6 Receptor antagonists. A new pharmacophore model of 5-HT6 Receptor antagonists was proposed based on the structure—5-HT6 antagonist activity relationship. It was established that the activity of the synthesized compounds depended strongly on the nature of the amine located vicinal to the sulfonyl. The most active ligands were methyl-(4-phenylsulfonyloxazol-5-yl)amines. Replacing the methyl by a bulkier alkyl radical and conversion to tertiary amines was accompanied by a dramatic reduction of their activity for 5-HT6 Receptors.

  • 5-HT6 Receptor antagonists. I. Screening of the library of various heterocyclic compounds containing an alkylsulfonyl moiety
    Pharmaceutical Chemistry Journal, 2012
    Co-Authors: Alexandre V. Ivachtchenko, E. S. Golovina, Madina G. Kadieva, Oleg D. Mitkin, Sergey E. Tkachenko, Ilya Okun

    Abstract:

    High-throughput screening of a specific set (focused library) of heterocyclic compounds containing an alkylsulfonyl moiety (a total of 2827 compounds from 78 combinatorial libraries) was performed in order to discover highly effective 5-HT6 Receptor antagonists. The screening identified several compounds that exhibited pronounced inhibiting properties for 5-HT6 Receptors that enabled them to be used to develop new highly effective drugs for treating central nervous system disturbances. The structures of most antagonists corresponded to the PhM2 pharmacophore model, which confirmed its potential in the search for effective 5-HT6 Receptor antagonists. It was established that the structure of the substituent introduced in the vicinity of the sulfonyl moiety in the PhM2 ligands could affect their pharmacological activity, including the ability to block serotonin-induced 5-HT6 Receptor-mediated cell responses. In particular, bulky electron-donating substituents decreased the activity whereas a methylamino group increased statistically significantly the 5-HT6 antagonistic activity. Based on these findings, a new pharmacophore model for 5-HT6 antagonists, PhM3, was proposed. It was shown that compounds from the combinatorial libraries with a sulfonyl moiety separated from the heterocyclic and/or aromatic moiety by one (or more) methylenes and heterocyclic compounds containing an alkylsulfonyl moiety or endocyclic sulfonyl, (5-aryl-sulfonyl-3H-[1,2,3]triazol-4-yl)amines, and azoles substituted simultaneously by arylsulfonyl and alkylsulfonyl moieties all had low hit rates and were not promising for discovery of new 5-HT6 Receptor antagonists.

  • synthesis and structure activity relationship sar of 5 7 disubstituted 3 phenylsulfonyl pyrazolo 1 5 a pyrimidin 2 yl methylamines as potent serotonin 5 ht6 Receptor 5 ht6r antagonists
    Journal of Medicinal Chemistry, 2011
    Co-Authors: Alexandre V. Ivachtchenko, Sergey E. Tkachenko, Elena S Golovina, M G Kadieva, Volodymyr Kysil, Oleg Dmitrievich Mitkin, Ilya Matusovich Okun

    Abstract:

    Syntheses, biological evaluation as 5-HT6 Receptor (5-HT6R) antagonists, and structure–activity relationships for a series of novel 5,7-disubstituted (3-arylsulfonyl-pyrazolo[1,5-a]pyrimidins are disclosed. The molecule conformational flexibility in the series is restricted by formation of the intramolecular hydrogen bond between 3-sulfo and 2-methylamino groups, which renders high potency and high selectivity to block serotonin-induced responses in HEK-293 cells stably expressing human 5-HT6R. In this work, we tested the hypothesis if addition of a positively ionizable group (PI) to the pyrimidine ring of the scaffold members in positions 5, 6, or 7 could further increase their 5HT6R blocking potency. We show that the presence of the PI group with small substituents does not substantially affect either potency or selectivity of the ligands while causing substantial changes in their cLogP values. This provides a possibility for designing of the 5HT6R ligands with modified ADME characteristics without gros…

María J. Ramírez – One of the best experts on this subject based on the ideXlab platform.

  • Serotonin 5-HT6 Receptor Antagonists in Alzheimer’s Disease: Therapeutic Rationale and Current Development Status.
    CNS Drugs, 2016
    Co-Authors: Hilda Ferrero, Maite Solas, Paul T. Francis, María J. Ramírez

    Abstract:

    Alzheimer’s disease (AD) is the most common cause of dementia in elderly people. Because of the lack of effective treatments for this illness, research focused on identifying compounds that restore cognition and functional impairments in patients with AD is a very active field. Since its discovery in 1993, the serotonin 5-HT6 Receptor has received increasing attention, and a growing number of studies supported 5-HT6 Receptor antagonism as a target for improving cognitive dysfunction in AD. This article reviews the rationale behind investigations into the targeting of 5-HT6 Receptors as a symptomatic treatment for cognitive and/or behavioral symptoms of AD. In addition to describing the available clinical evidence, this article also describes the purported biochemical and neurochemical mechanisms of action by which 5-HT6 Receptor antagonists could influence cognition, and the preclinical data supporting this therapeutic approach to AD. A large number of publications describing the development of ligands for this Receptor have come to light and preclinical data indicate the procognitive efficacy of 5-HT6 Receptor antagonists. Subsequently, the number of patents protecting 5-HT6 chemical entities has continuously grown. Some of these compounds have successfully undergone phase I clinical studies and have been further evaluated in clinical phase II trials with variable success. Phase II studies have also revealed the potential of combining 5-HT6 Receptor antagonism and cholinesterase inhibition. Two of these antagonists, idalopirdine and RVT-101, have been further developed into ongoing phase III clinical trials. Overall, 5-HT6 Receptor antagonists can reasonably be regarded as potential drug candidates for the treatment of AD.

  • 5-HT6 Receptors and Alzheimer’s disease.
    Alzheimer's Research & Therapy, 2013
    Co-Authors: María J. Ramírez

    Abstract:

    During the past 20 years, the 5-HT6 Receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 Receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this Receptor have come to light, and it is now quite evident that 5-HT6 Receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 Receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 Receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 Receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer’s disease.

  • 5-HT6 Receptor signal transduction second messenger systems.
    International Review of Neurobiology, 2010
    Co-Authors: Xavier Codony, Javier Burgueño, María J. Ramírez, José Miguel Vela

    Abstract:

    Publisher Summary The 5-HT6 Receptor belongs to the G-protein-coupled Receptor (GPCR) family. This chapter reviews some reported experimental approaches that can be used for a better functional characterization and classification of 5-HT6 Receptor ligands. The chapter summarizes the results obtained using some representative 5-HT6 Receptor agonists and antagonists. 5-HT6 Receptor functionality is being revealed to be much more complex than initially defined. Based on the existing data and depending on the agonist used, different selective Receptor active states that activate different cellular pathways may be achieved. Besides Gs-mediated cAMP formation, other messenger systems may be involved. The full characterization of the functional profile of 5-HT6 Receptor is still pending, and new players in the signaling cascade of 5-HT6 Receptor could take the stage in the near future.

Ohdong Hwan – One of the best experts on this subject based on the ideXlab platform.

  • antistress effects of rosa rugosa thunb on total sleep deprivation induced anxiety like behavior and cognitive dysfunction in rat possible mechanism of action of 5 ht6 Receptor antagonist
    Journal of Medicinal Food, 2016
    Co-Authors: Ohdong Hwan

    Abstract:

    Abstract Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation–induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) Receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) Receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 Receptor and resulting inhibition of cAMP activity.

  • Antistress Effects of Rosa rugosa Thunb. on Total Sleep Deprivation–Induced Anxiety-Like Behavior and Cognitive Dysfunction in Rat: Possible Mechanism of Action of 5-HT6 Receptor Antagonist
    Journal of Medicinal Food, 2016
    Co-Authors: Naju-ryun, Ohdong Hwan, Ohdool-ri, Hanseulhee, Kimyu-jin, Choieunjin, Baedonghyuck, Leeyoo-hyun, Kimsunoh, Junwoojin

    Abstract:

    Abstract Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation–induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) Receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) Receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 Receptor and resulting inhibition of cAMP activity.