Combined 5-HT2A and mGlu2 modulation for the treatment of dyskinesia and psychosis in Parkinson's disease

Kwan, Cynthia; Frouni, Imane; Nuara, Stephen G.; Belliveau, Sébastien; Kang, Woojin; Hamadjida, Adjia; Bédard, Dominique; Beaudry, Francis; Panisset, Michel; Gourdon, Jim C.

doi:10.1016/j.neuropharm.2021.108465

Cited by 15 publications

(5 citation statements)

References 42 publications

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“…It is known that drugs are absorbed slowly and their half-lives are relatively longer because the lymphatic flow rate is slow (37,38). As the drug hydrophobicity is increased, T max values after single SC doses of small-molecule drugs to rats increased as follows: within 0.08 h for radiolabeled 14 C-sumatriptan succinate (sumatriptan's logP = 0.93), 0.117 ± 0.017, 0.167 ± 0.017, 0.250 ± 0 h for ondansetron (logP = 2.40), and 0.5 h for risperidone (logP = 3.27) (39)(40)(41). A similar trend was observed in the results of SC administration in the present study.…”

Section: Discussionmentioning

confidence: 99%

Intradermal Administration of Rescue Dose of Antiemetics in Chemotherapy-induced Nausea and Vomiting

Maekawa-Matsuura,

Shimizu,

Sakamaki

et al. 2023

Preprint

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Antiemetic therapy is provided to patients with cancer to prevent chemotherapy- induced nausea and vomiting (CINV), based on the emetic risk of anticancer agents. However, breakthrough CINV can occur despite appropriate antiemetic prophylaxis. It is preferable to administer the rescue dose of antiemetics in breakthrough CINV that occur at home, in a form that is immediately effective and that can be easily self- administered by the patient. In the present study, we examined and compared the blood pharmacokinetics of subcutaneous (SC) injection, a preferred route of self-injection, and intradermal (ID) injection, a less invasive route, with an aim of developing simple self- injectable rescue antiemetics. A single administration of four kinds of antiemetics via SC and ID routes in rats resulted in lowerTmaxvalues compared with previously reported oral administration, indicating that the administration of antiemetics via ID and SC routes may be effective in providing faster antiemetic effects and to alleviate patient symptoms.

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Section: Discussionmentioning

confidence: 99%

Intradermal Administration of Rescue Dose of Antiemetics in Chemotherapy-induced Nausea and Vomiting

Maekawa-Matsuura,

Shimizu,

Sakamaki

et al. 2023

Preprint

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“…In recent years, modern medical research has shown that the pathogenesis of PD is complex and involves multiple factors. Past experiments have shown that the pathological changes in PD involve not only dopaminergic neurons in the substantia nigra and striatum system but also involve other parts of the dopaminergic system and the 5-hydroxytryptamergic, norepinephrinergic, and cholinergic systems, as well as the dynorphin, enkephalin, and other peptide transmitter systems [26][27][28].…”

Section: The Role Of Sch a In Diseasesmentioning

confidence: 99%

Research Progress on the Pharmacological Action of Schisantherin A

Xiao

2022

Evidence-Based Complementary and Alternative Medicine

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Schisantherin A (Sch A) is a dibenzocyclooctadiene lignan monomer isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (S. chinensis). At present, many studies have shown that Sch A has a wide range of pharmacological effects, including its anti-Parkinson and anti-inflammatory effects and ability to protect the liver, protect against ischemia-reperfusion (I/R) injury, suppress osteoclast formation, and improve learning and memory. Its mechanism may be related to the antioxidant, anti-inflammatory, and antiapoptotic properties of Sch A through the MAPK, NF-κB, AKT/GSK3β, and PI3K/AKT pathways. This is the first review of the recent studies on the pharmacological mechanism of Sch A.

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“…These heterodimers include mGluR/serotonin 5-HT 2A receptor (5-HT 2A R), mGlu5/adenosine A 2A R (A2AR), Glu5/dopamine D1 receptor (D1R), and mGlu5/mu-opioid receptor (MOR) [26,[67][68][69][70][71][72]. Among these heterodimers, mGlu2/5-HT 2A R is the most widely investigated and association to the pathophysiology of psychosis in schizophrenia and Parkinson's disease, as well as dyskinesia in the latter rendered this heterodimer an attractive target for the treatment of these diseases [68][69][70]73].…”

Section: Altered Gpcr Activities Induced Through Heterodimerizationmentioning

confidence: 99%

Structural Characterization of Receptor–Receptor Interactions in the Allosteric Modulation of G Protein-Coupled Receptor (GPCR) Dimers

Lazim¹,

Suh²,

Lee³

et al. 2021

IJMS

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G protein-coupled receptor (GPCR) oligomerization, while contentious, continues to attract the attention of researchers. Numerous experimental investigations have validated the presence of GPCR dimers, and the relevance of dimerization in the effectuation of physiological functions intensifies the attractiveness of this concept as a potential therapeutic target. GPCRs, as a single entity, have been the main source of scrutiny for drug design objectives for multiple diseases such as cancer, inflammation, cardiac, and respiratory diseases. The existence of dimers broadens the research scope of GPCR functions, revealing new signaling pathways that can be targeted for disease pathogenesis that have not previously been reported when GPCRs were only viewed in their monomeric form. This review will highlight several aspects of GPCR dimerization, which include a summary of the structural elucidation of the allosteric modulation of class C GPCR activation offered through recent solutions to the three-dimensional, full-length structures of metabotropic glutamate receptor and γ-aminobutyric acid B receptor as well as the role of dimerization in the modification of GPCR function and allostery. With the growing influence of computational methods in the study of GPCRs, we will also be reviewing recent computational tools that have been utilized to map protein–protein interactions (PPI).

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Combined 5-HT2A and mGlu2 modulation for the treatment of dyskinesia and psychosis in Parkinson's disease

Cited by 15 publications

References 42 publications

Intradermal Administration of Rescue Dose of Antiemetics in Chemotherapy-induced Nausea and Vomiting

Intradermal Administration of Rescue Dose of Antiemetics in Chemotherapy-induced Nausea and Vomiting

Research Progress on the Pharmacological Action of Schisantherin A

Structural Characterization of Receptor–Receptor Interactions in the Allosteric Modulation of G Protein-Coupled Receptor (GPCR) Dimers

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