Employing two different alkyne-modified dopamine agonists to construct bivalent compounds via click chemistry resulted in the identification of a bivalent ligand (11c) for dopamine D receptor homodimer, which, compared to its parent monomeric alkyne, showed a 16-fold higher binding affinity for the dopamine D receptor and a 5-fold higher potency in a cAMP assay in HEK 293T cells stably expressing DR. Molecular modeling revealed that 11c can indeed bridge the orthosteric binding sites of a DR homodimer in a relaxed conformation via the TM5-TM6 interface and allows to largely rationalize the results of the receptor assays.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2020.113151 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Co-Expression of Tardive Dyskinesia and Drug-Induced Parkinsonism in Rats Chronically Treated With Haloperidol.
Neuropsychopharmacol Rep
March 2025
Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Aim: We aimed to create a rat model of drug-induced parkinsonism and tardive dyskinesia by chronic administration of haloperidol and examine the expression of direct and indirect pathway markers in the striatum of the model rats.
Methods: We treated 21 rats, 14 with haloperidol decanoate and 7 with placebo. The number of vacuous chewing movements per 2 min was counted, and haloperidol-treated rats were classified into two groups: mild and severe tardive dyskinesia.
Gestational stress disrupts dopamine and oxytocin signaling in the postpartum reward system of rats: implications for mood, motivation and mothering.
Sci Rep
January 2025
Neuroscience Graduate Program, The Ohio State University, Columbus, OH, 43210, USA.
Postpartum depression (PPD) affects up to 20% of new mothers and has adverse consequences for the well-being of both mother and child. Exposure to stress during pregnancy as well as dysregulation in the mesolimbic dopamine (DA) reward system and its upstream modulator oxytocin (OT) have been independently linked to PPD. However, no studies have directly examined DA or OT signaling in the postpartum brain after gestational stress.
View Article and Find Full Text PDFAdvances in pharmacological treatment of Cushings disease.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology ＆Metabolism, West China Hospital, Sichuan University, Chengdu 610041.
Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.
View Article and Find Full Text PDFDeficiency of histamine H receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention.
Neuron
January 2025
Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:
Attention deficit hyperactivity disorder (ADHD), affecting 4% of the population, is characterized by inattention, hyperactivity, and impulsivity; however, its neurophysiological mechanisms remain unclear. Here, we discovered that deficiency of histamine H receptor (HR) in parvalbumin-positive neurons in substantia nigra pars recticulata (PV) attenuates PV neuronal activity and induces hyperactivity, impulsivity, and inattention in mice. Moreover, decreased HR expression was observed in PV in patients with ADHD symptoms and dopamine-transporter-deficient mice, whose behavioral phenotypes were alleviated by HR agonist treatment.
View Article and Find Full Text PDFPopulation pharmacokinetics of blonanserin in Japanese adolescent and adult patients with schizophrenia.
Drug Metab Pharmacokinet
November 2024
Clinical Research, Drug Development Division, Sumitomo Pharma Co., Ltd., 33-94, Enoki-cho, Suita, Osaka, 564-0053, Japan. Electronic address:
The second-generation antipsychotic blonanserin is a highly selective, full antagonist of dopamine D and D and serotonin 5-HT receptors. It is currently prescribed for patients with schizophrenia in Japan. We aimed to develop a population pharmacokinetic model of oral blonanserin, including data from 12 to 77 years old patients, to assess the covariates that influence blonanserin pharmacokinetics and evaluate appropriate dosage regimens in adolescents versus adults.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!