Although evidence suggests that 5-HT(2A) and muscarinic M1/M4 receptors are implicated in the pathology of schizophrenia, the results are not conclusive. In the present study we tested the hypothesis that binding of 5-HT(2A) and M1/M4 receptors is altered in the postmortem brain of schizophrenia subjects. Quantitative autoradiography was employed to measure [(3)H]ketanserin binding to 5-HT(2A) receptors and [(3)H]pirenzepine binding to both M1 and M4 receptors in Brodmann's area 9 (BA9), caudate/putamen, and the hippocampal formation from six schizophrenic and six control subjects. A significant reduction in the density of 5HT(2A) receptors in BA 9 of schizophrenic subjects was observed (p=0.036). No significant difference was observed in the density of 5HT(2A) receptors in the hippocampus or caudate/putamen between the two groups. No significant changes in the density of M1/M4 receptors was observed in these three regions between the two groups. These findings support a possible involvement of the serotonergic system in the pathology of schizophrenia.
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http://dx.doi.org/10.1016/j.neulet.2004.12.059 | DOI Listing |
JAMA Psychiatry
August 2024
Karuna Therapeutics, Boston, Massachusetts.
Med Res Rev
September 2024
Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
Despite extensive research efforts aimed at discovering novel antipsychotic compounds, a satisfactory pharmacological strategy for schizophrenia treatment remains elusive. All the currently available drugs act by modulating dopaminergic neurotransmission, leading to insufficient management of the negative and cognitive symptoms of the disorder. Due to these challenges, several attempts have been made to design agents with innovative, non-dopaminergic mechanisms of action.
View Article and Find Full Text PDFBioorg Med Chem
May 2024
School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, PR China.. Electronic address:
Muscarinic acetylcholine receptors (mAChRs) play a significant role in the pathophysiology of schizophrenia. Although activating mAChRs holds potential in addressing the full range of schizophrenia symptoms, clinical application of many non-selective mAChR agonists in cognitive deficits, positive and negative symptoms is hindered by peripheral side effects (gastrointestinal disturbances and cardiovascular effects) and dosage restrictions. Ligands binding to the allosteric sites of mAChRs, particularly the M1 and M4 subtypes, demonstrate activity in improving cognitive function and amelioration of positive and negative symptoms associated with schizophrenia, enhancing our understanding of schizophrenia.
View Article and Find Full Text PDFCurr Drug Discov Technol
April 2024
Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Piparia, Vadodara, Gujarat, India.
Background: VEGFR-2 tyrosine kinase inhibitors are receiving a lot of attention as prospective anticancer medications in the current drug discovery process.
Objective: This work aims to explore the PubChem library for novel VEGFR-2 kinase inhibitors. 1H-Indazole-containing drug AXITINIB, or AG-013736 (FDA approved), is chosen as a rational molecule for drug design.
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