The 5-HT2A receptor ligand 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) selectively binds to human (h) and rat 5-HT2A receptors (IC50 values 0.35 and 1 nM, respectively; vs. 1334 nM for h5-HT2C) and inhibited 5-HT-stimulated [35S]guanosine 5'-O-3-thiotriphosphate (GTPgammaS)-accumulation in h5-HT2A transfected Chinese hamster ovary cells (IC50 9.3 nM). EMD 28014 counteracted the N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)-induced decrease of [3H]ketanserin binding in rat frontal cortex (ID50 0.4 mg/kg p.o.) and R-(-)-1-(2,5-dimethoxy-4-iodophenyl)-aminopropane (DOI)-induced head-twitch behaviour in mice (ID50 0.01 mg/kg s.c., 0.06 mg/kg p.o.), demonstrating unique selectivity and efficacy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0014-2999(03)01992-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effects of low-doses of methamphetamine on d-fenfluramine-induced head-twitch response (HTR) in mice during ageing and c-fos expression in the prefrontal cortex.
BMC Neurosci
January 2023
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, CA, 91766, USA.
Background: The head-twitch response (HTR) in mice is considered a behavioral model for hallucinogens and serotonin 5-HT receptor function, as well as Tourette syndrome in humans. It is mediated by 5-HT receptor agonists such as ( ±)- 2,5-dimethoxy-4-iodoamphetamine (DOI) in the prefrontal cortex (PFC). The 5-HT antagonist EMD 281014, can prevent both DOI-induced HTR during ageing and c-fos expression in different regions of PFC.
View Article and Find Full Text PDFAn ontogenic study of receptor mechanisms by which acute administration of low-doses of methamphetamine suppresses DOI-induced 5-HT-receptor mediated head-twitch response in mice.
BMC Neurosci
January 2022
Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, 309 East Second Street, Pomona, CA, 91766, USA.
Background: Methamphetamine (MA) is a non-selective monoamine releaser and thus releases serotonin (5-HT), norepinephrine (NE) and dopamine (DA) from corresponding nerve terminals into synapses. DOI ((±)-2, 5-dimethoxy-4-iodoamphetamine) is a direct-acting serotonergic 5-HT receptor agonist and induces the head-twitch response (HTR) via stimulation of 5-HT receptor in mice. While more selective serotonin releasers such as d-fenfluramine evoke the HTR, monoamine reuptake blockers (e.
View Article and Find Full Text PDFAdditive effects of mGluR positive allosteric modulation, mGluR orthosteric stimulation and 5-HTR antagonism on dyskinesia and psychosis-like behaviours in the MPTP-lesioned marmoset.
Naunyn Schmiedebergs Arch Pharmacol
December 2021
Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), 3801 University St, Montreal, QC, H3A 2B4, Canada.
Purpose: Antagonising serotonin (5-HT) type 2A receptors (5-HTR) is an effective strategy to alleviate both dyskinesia and psychosis in Parkinson's disease (PD). We have recently shown that activation of metabotropic glutamate 2 receptors (mGluR), via either orthosteric stimulation or positive allosteric modulation, enhances the anti-dyskinetic and anti-psychotic effects of 5-HTR antagonism. Here, we investigated if greater therapeutic efficacy would be achieved by combining 5-HTR antagonism with concurrent mGluR orthosteric stimulation and mGluR positive allosteric modulation.
View Article and Find Full Text PDFCombined 5-HT and mGlu modulation for the treatment of dyskinesia and psychosis in Parkinson's disease.
Neuropharmacology
March 2021
Neurodegenerative Disease Group, Montreal Neurological Institute, Montreal, QC, Canada; Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, QC, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada; Movement Disorder Clinic, Division of Neurology, Department of Neuroscience, McGill University Health Centre, Montreal, QC, Canada. Electronic address:
Article Synopsis
- Concurrent antagonism of the serotonin 2A receptor and activation of mGlu receptors can significantly reduce dyskinesia and psychosis in Parkinson’s disease beyond the effects of each treatment alone.
- The study involved multiple experiments on MPTP-lesioned marmosets, testing combinations of a mGlu positive allosteric modulator and a 5-HT antagonist alongside L-DOPA.
- Results showed substantial improvements in both anti-dyskinetic and anti-psychotic outcomes with combined treatments compared to single treatments, indicating a potentially more effective therapeutic strategy for managing Parkinson’s disease symptoms.
5-HT blockade for dyskinesia and psychosis in Parkinson's disease: is there a limit to the efficacy of this approach? A study in the MPTP-lesioned marmoset and a literature mini-review.
Exp Brain Res
February 2019
Neurodegenerative Disease Group, Montreal Neurological Institute, 3801 University St, BT 209, Montreal, QC, H3A 2B4, Canada.
Virtually every patient affected by Parkinson's disease (PD) eventually requires treatment with L-3,4-dihydroxyphenylalanine (L-DOPA), which leads to complications such as dyskinesia and psychosis. Whereas blockade of serotonin 2A (5-HT) receptors appears to be an effective way to reduce both dyskinesia and psychosis, whether it has the potential to eliminate the two phenomena remains to be determined. In a previous study, we showed that highly selective 5-HT receptor blockade with EMD-281,014, at plasma levels comparable to those achieved in the clinic, reduced dyskinesia and psychosis-like behaviours (PLBs), in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset.
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!