Identification of Benzopyran‐4‐one Derivatives (Isoflavones) as Positive Modulators of GABA<sub>A</sub> Receptors

Chemotherapy-induced nausea and vomiting and postoperative nausea and vomiting are one of the most frequent but also very concerning consequences for patients undergoing chemotherapy or surgical procedures under general anesthesia. There are a variety of mechanisms involved in the activation of nausea and vomiting. Serotonin, a ubiquitous central and peripheral neurotransmitter, is thought to be the predominant mediator of the perception of nausea and triggering of the vomiting response in both the brain and the periphery via the 5-hydroxytryptamine type 3 (5-HT3) receptor pathways. 5-HT3 receptor antagonists disrupt this pathway, largely at the level of the vagal afferent pathways, to decrease nausea and vomiting. This review will focus on dolasetron, an older but sill commonly used 5-HT3 receptor antagonist and its multimodal mechanism of action, safety and tolerability, patient considerations, and a review of the current literature on its use to combat both chemotherapy-induced and postoperative nausea and vomiting in these two important patient populations.

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“…Flumazenil-insensitive modulation by the isoflavones suggested that these compounds might not bind to the benzodiazepine binding site. 118 …”

Section: Synthetic Derivatives: Importance Of 6-substitutions On the mentioning

confidence: 99%

Flavonoids as GABAA receptor ligands: the whole story?

Wasowski

Marder

2012

JEP

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“…Later on, GABA was confirmed to be one of the foremost inhibitory neurotransmitters in the spinal dorsal horn (Yaksh, 1989). After release from the pre-synaptic neurons, GABA act postsynaptically upon 3 major classes of receptors namely; GABA A and GABA C receptors that are ligandgated ion channels and GABA B that are G proteincoupled channels (Gavande et al, 2011). Chemically ionotropic GABA A receptors are formed of transmembrane protein complexes and comprise 5 heteropentameric subunits.…”

Section: Role Of Gaba In Neuropathic Painmentioning

confidence: 99%

Flavonoids in neuropathic pain management: A new player on an old target

Akbar¹

2019

Afr. J. Pharm. Pharmacol.

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Neuropathic pain is the consequence of abnormal processing in the peripheral or central nervous system (CNS) elicited by neuronal injury. Due to its heterogeneous nature and important unwanted adverse effects of the commonly prescribed psychoactive drugs like benzodiazepines (BDZ), the treatment of neuropathic pain has remained a challenge for the scientific community. Flavonoids initially isolated from plants and used as tranquilizers in Folkloric medicine, have been reported to possess selective affinity for BDZ binding site. These positive ionotropic modulators of γ-amino butyric acid-A (GABA A) receptors enhance the chloride ion flux and provide a strong inhibitory effect. Therefore, for the treatment of central nervous system-related disorders such as neuropathic pain, these selective GABA A receptor modulators stand amongst the strongest candidates. This review provides an update on research development that has confirmed the activity of different flavonoids on GABA A receptors.

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“…Bearing in mind the construction of the isoflavone core by a possible scalable synthesis, Felpin and co-workers [161] bed on a solution-phase Suzuki reaction using Pd(0)/C as heterogenous practical and inexpensive catalyst under ligand-free conditions, which was then used by other authors (Scheme 38) [162,163]. Beyond the excellent yields of cross-coupled products 114, the heterogeneous nature of the catalyst is extremely well suited for large-scale applications.…”

Section: Reactivity Of 3-halochromonesmentioning

confidence: 99%