Abstract
It is well accepted that acetylcholine is involved in memory and learning processes and that loss of memory is characteristic of Alzheimers disease (AD). Several muscarinic agonists have been shown to be clinically effective in the treatment of AD. However, their use has been limited due to adverse side effects. As a result, more selective M1 agonists are expected to be the next generation of agents for the treatment of AD. One pharmacological approach to evaluate possible cognitive effects of compounds includes their ability to reverse scopolamine-induced amnesia. In the current study the succinamide and succinimide of p-aminophenol, two newly synthesized compounds that were previously designed to be acetylcholine analogues, were evaluated in a Pavlovian/Instrumental autoshaped memory task. Simultaneously, docking studies on the M1 receptor were done. The scopolamine-induced amnesia was reversed by the amide but not the imide. These findings are in line with results derived from the docking simulations, and suggest that at least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.
Keywords: Succinic acid, p-aminophenol, scopolamine, allosteric, docking simulations, Alzheimer's disease, memory
Medicinal Chemistry
Title: Effect of a M1 Allosteric Modulator on Scopolamine-Induced Amnesia
Volume: 3 Issue: 1
Author(s): J. Espinosa-Raya, M. Espinoza-Fonseca, O. Picazo and J. Trujillo-Ferrara
Affiliation:
Keywords: Succinic acid, p-aminophenol, scopolamine, allosteric, docking simulations, Alzheimer's disease, memory
Abstract: It is well accepted that acetylcholine is involved in memory and learning processes and that loss of memory is characteristic of Alzheimers disease (AD). Several muscarinic agonists have been shown to be clinically effective in the treatment of AD. However, their use has been limited due to adverse side effects. As a result, more selective M1 agonists are expected to be the next generation of agents for the treatment of AD. One pharmacological approach to evaluate possible cognitive effects of compounds includes their ability to reverse scopolamine-induced amnesia. In the current study the succinamide and succinimide of p-aminophenol, two newly synthesized compounds that were previously designed to be acetylcholine analogues, were evaluated in a Pavlovian/Instrumental autoshaped memory task. Simultaneously, docking studies on the M1 receptor were done. The scopolamine-induced amnesia was reversed by the amide but not the imide. These findings are in line with results derived from the docking simulations, and suggest that at least the succinamide of p-aminophenol could represent a novel candidate for the treatment of AD.
Export Options
About this article
Cite this article as:
Espinosa-Raya J., Espinoza-Fonseca M., Picazo O. and Trujillo-Ferrara J., Effect of a M1 Allosteric Modulator on Scopolamine-Induced Amnesia, Medicinal Chemistry 2007; 3 (1) . https://dx.doi.org/10.2174/157340607779317526
DOI https://dx.doi.org/10.2174/157340607779317526 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Polypharmacology of <i>Aconitum</i> and <i>Delphinium</i> sp. Diterpene Alka loids: Antiarrhythmic, Analgesic and Anti-Inflammatory Effects
Mini-Reviews in Organic Chemistry Targeting Parkinson’s - Tyrosine Hydroxylase and Oxidative Stress as Points of Interventions
CNS & Neurological Disorders - Drug Targets The Use of Quetiapine for Comorbid Bipolar and Obsessive Compulsive Disorders
Current Psychopharmacology Investigating the Link between Psoriasis and Cardiovascular Disease: Current Evidence, Therapeutic Implications and Perspectives
Current Vascular Pharmacology Binding Site Detection and Druggability Prediction of Protein Targets for Structure- Based Drug Design
Current Pharmaceutical Design Sigma-1 Receptors: Potential Targets for the Treatment of Substance Abuse
Current Pharmaceutical Design Proteomic Comparison of the Aleurone Layer in Triticum Aestivum and Triticum Monococcum Wheat Varieties
Current Proteomics Diagnosis, Pathogenesis and Therapeutic Targets in Amyotrophic Lateral Sclerosis
CNS & Neurological Disorders - Drug Targets Oxidative RNA Damage and Neurodegeneration
Current Medicinal Chemistry The Sea Urchin, Paracentrotus lividus, as a Model to Investigate the Onset of Molecules Immunologically Related to the α-7 Subunit of Nicotinic Receptors During Embryonic and Larval Development
Current Drug Targets Perioperative Management of Obese Parturients
Current Women`s Health Reviews γ-AApeptides as a New Strategy for Therapeutic Development
Current Medicinal Chemistry Phytochemicals as Prototypes for Pharmaceutical Leads Towards Drug Development Against Diabetic Cardiomyopathy
Current Pharmaceutical Design Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?
Central Nervous System Agents in Medicinal Chemistry Aromatic Sulfur Compounds Enrichment from Seawater in Crude Oil Contamination by Solid Phase Extraction
Current Analytical Chemistry Inhibition of Neurogenesis by Zika Virus Infection
CNS & Neurological Disorders - Drug Targets TRYCAT Pathways Link Peripheral Inflammation, Nicotine, Somatization and Depression in the Etiology and Course of Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Genetic Transmission of Cytochrome P450 2D6 (CYP2D6) Ultrarapid Metabolism: Implications for Breastfeeding Women taking Codeine
Current Drug Safety Can Life Before Birth Affect Health Ever After?
Current Women`s Health Reviews Buprenorphine and Buprenorphine/Naloxone Intoxication in Children – How Strong is the Risk?
Current Drug Abuse Reviews