Background/objectives: Antipsychotic medicines are used to treat several psychological disorders and some symptoms caused by dementia and schizophrenia. Haloperidol (Hal) is a typical antipsychotic usually used to treat psychosis; however, its use causes motor or extrapyramidal symptoms (EPS) such as catalepsy. Hal blocks the function of presynaptic D2 receptors on cholinergic interneurons, leading to the release of acetylcholine (ACh), which is hydrolyzed by the enzyme acetylcholinesterase (AChE).
Methods: This study was designed to investigate the Hal-inhibitory effects on AChE activity in regions representative of the cholinergic system of mice and potential associations between cataleptic effects generated by Hal using therapeutic doses and their inhibitory effects on AChE.
Results: The distribution of the AChE activity in the different regions of the brain followed the order striatum > hippocampus > (prefrontal cortex/hypothalamus/ cerebellum) > brainstem > septo-hippocampal system. In ex vivo assays, Hal inhibited AChE activity obtained from homogenate tissue of the striatum, hippocampus, and septo-hippocampal system in a concentration-dependent manner. The inhibitory concentration of 50% of enzyme activity (IC) indicated that the septo-hippocampal system required a higher concentration of Hal (IC = 202.5 µmol·L) to inhibit AChE activity compared to the striatum (IC = 162.5 µmol·L) and hippocampus (IC = 145 µmol·L). In in vivo assays, male Swiss mice treated with concentrations of Hal higher than 0.1 mg·kg induced cataleptic effects. Positive correlations with were observed only between the lack of cataleptic effect and the decreased AChE activity of the hippocampus in the mice treated with 0.01 mg·kg of Hal but not in the striatum and septo-hippocampal system.
Conclusions: Our results suggest that Hal could increase cholinergic effects via AChE inhibition, in addition to its dopamine antagonist effect, as an alternative approach to the treatment of behavioral disturbances associated with dementia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11678777 | PMC |
| http://dx.doi.org/10.3390/neurolint16060125 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Diagnosis and Treatment Options for Cirrhosis With Unexplained Upper Gastrointestinal Bleeding: An Observational Study Based on Endoscopic Ultrasonography.
Surg Laparosc Endosc Percutan Tech
January 2025
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Diseases of Anhui Province, Hefei, Anhui, China.
Objective: To investigate the role of endoscopic ultrasonography (EUS) in the diagnosis and treatment of upper gastrointestinal bleeding of unknown origin in liver cirrhosis, focusing on patients with recurrent treatment of esophageal and gastric varices who failed to identify the bleeding site under direct endoscopy.
Background: Esophagogastric variceal bleeding is one of the severe complications of decompensated liver cirrhosis, and serial endoscopic therapy can improve the long-term quality of life of patients. Most acute bleeding can be detected under direct endoscopy with thrombus or active bleeding, but there are still some patients with recurrent bleeding after repeated treatments, and it is difficult to find the bleeding site, especially in gastric variceal bleeding.
Unlocking Platelet Mechanisms through Multi-Omics Integration: A Brief Review.
Curr Cardiol Rev
January 2025
Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University, Saint-Petersburg, Russian Federation.
Platelets, tiny cell fragments measuring 2-4 μm in diameter without a nucleus, play a crucial role in blood clotting and maintaining vascular integrity. Abnormalities in platelets, whether genetic or acquired, are linked to bleeding disorders, increased risk of blood clots, and cardiovascular diseases. Advanced proteomic techniques offer profound insights into the roles of platelets in hemostasis and their involvement in processes such as inflammation, metastasis, and thrombosis.
View Article and Find Full Text PDFThe role of cancer cell-released extracellular vesicles: have we become closer to cancer pain treatment?
Extracell Vesicles Circ Nucl Acids
December 2024
Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
The effective management of cancer pain continues to be a challenge because of our limited understanding of cancer pain mechanisms and, in particular, how cancer cells interact with neurons to produce pain. In a study published in , Inyang used a mouse model of human papillomavirus (HPV1)-induced oropharyngeal squamous cell carcinoma to show a role for cancer cell-derived extracellular vesicles (cancer sEVs) in cancer pain. They found that inhibiting the release of sEVs reduced spontaneous and evoked pain behaviors, and that pain produced by sEVs is due to activation of TRPV1 channels.
View Article and Find Full Text PDFObesity and the Importance of Breathing.
Cureus
January 2025
Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, USA.
Obesity is a complex and non-communicable disease with a pandemic entity. Currently, multiple causes can lead to obesity, and it is not always easy to create a direct relationship between physical inactivity, poor quality of nutrients consumed, and calculation of excess calories. Among the associated comorbidities, obesity creates a dysfunctional environment of respiratory rhythms at the central and peripheral levels, with functional, morphological, and phenotypic alteration of the diaphragm muscle.
View Article and Find Full Text PDFAtypical Lesions in Virchow-Robin Spaces: A Case Report.
Cureus
January 2025
Anesthesiology, Universidad Abierta Interamericana, Buenos Aires, ARG.
The differentiation between benign and malignant brain lesions remains a fundamental challenge in modern neuroimaging. This case highlights a rare presentation of ectatic Virchow-Robin spaces (VRS), which mimicked tumefactive brain lesions and required a comprehensive diagnostic evaluation to exclude neoplastic, infectious, and inflammatory processes. A 37-year-old female presented with progressive headache, cognitive impairment, and facial pain.
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!