Abstract
During the last years the development of approaches to multitarget drug design and discovery is gaining acceptance. The cannabinoids are potentially excellent multi-target drug candidates because of their interesting pharmacological profiles, among which stands out the dual capacity of cannabinoid ligands to act as cannabinoid agonist and cholinesterase inhibitors. In this article, inhibition, kinetics studies and docking simulations with a representative set of cannabinoids are presented. The results of these studies showed the inhibitory capacity of some agonist cannabinoids with selectivity at AChE or BuChE enzymes. The kinetic and modelling studies allowed us to postulate the potential mode of action and the binding site of the cannabinoids. In general, the studied cannabinoids showed a mixed type inhibition mode of action. The exception to this behaviour was found for the agonist CP-55,940 that showed a non-competitive inhibition, suggesting that this cannabinoid only binds to the peripheral site.
Keywords: Alzheimer disease, agonist cannabinoids, cholinesterase inhibitors, multitarget drugs
Current Alzheimer Research
Title:Multitarget Cannabinoids as Novel Strategy for Alzheimer Disease
Volume: 10 Issue: 3
Author(s): Pedro Gonzalez-Naranjo, Nuria E. Campillo, Concepcion Perez and Juan A. Paez
Affiliation:
Keywords: Alzheimer disease, agonist cannabinoids, cholinesterase inhibitors, multitarget drugs
Abstract: During the last years the development of approaches to multitarget drug design and discovery is gaining acceptance. The cannabinoids are potentially excellent multi-target drug candidates because of their interesting pharmacological profiles, among which stands out the dual capacity of cannabinoid ligands to act as cannabinoid agonist and cholinesterase inhibitors. In this article, inhibition, kinetics studies and docking simulations with a representative set of cannabinoids are presented. The results of these studies showed the inhibitory capacity of some agonist cannabinoids with selectivity at AChE or BuChE enzymes. The kinetic and modelling studies allowed us to postulate the potential mode of action and the binding site of the cannabinoids. In general, the studied cannabinoids showed a mixed type inhibition mode of action. The exception to this behaviour was found for the agonist CP-55,940 that showed a non-competitive inhibition, suggesting that this cannabinoid only binds to the peripheral site.
Export Options
About this article
Cite this article as:
Gonzalez-Naranjo Pedro, E. Campillo Nuria, Perez Concepcion and A. Paez Juan, Multitarget Cannabinoids as Novel Strategy for Alzheimer Disease, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030002
DOI https://dx.doi.org/10.2174/1567205011310030002 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
- 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
- Announcements
Related Articles
-
S-nitrosation/Denitrosation in Cardiovascular Pathologies: Facts and Concepts for the Rational Design of S-nitrosothiols
Current Pharmaceutical Design Nanotechnology Based Delivery Systems of Drugs Currently Used to Treat Alzheimer’s Disease
Nanoscience & Nanotechnology-Asia Current Status and Perspectives in Ceramide-Targeting Molecular Medicine
Current Pharmaceutical Design Alzheimer's Disease and the Routine Clinical Use of CSF Biomarkers
CNS & Neurological Disorders - Drug Targets Loss of Medial Septum Cholinergic Neurons in THY-Tau22 Mouse Model: What Links with tau Pathology?
Current Alzheimer Research Activated Immune System and Inflammation in Healthy Ageing: Relevance for Tryptophan and Neopterin Metabolism
Current Pharmaceutical Design Modulation of Inflammation as a Way of Delaying Alzheimer's Disease Progression: The Diet's Role
Current Alzheimer Research Effect of Brain-Derived Neurotrophic Factor (BDNF) Gene Variants on the Therapeutic Response and the Risk for Mood Disorders
Current Pharmacogenomics and Personalized Medicine Translocator Protein (TSPO) Role in Aging and Alzheimer’s Disease
Current Aging Science Stress-Induced Oxidative Changes in Brain
CNS & Neurological Disorders - Drug Targets Quality of Education and Memory Test Performance in Older Men: The New York University Paragraph Recall Test Normative Data
Current Alzheimer Research Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View
Current HIV Research Radiolabeled Sugars Used for PET and SPECT Imaging
Current Radiopharmaceuticals Clinical Use of Aspirin in Ischemic Heart Disease: Past, Present and Future
Current Pharmaceutical Design Genetic Contributors to Frontotemporal Lobar Degeneration: Beyond Monogenic Disease
Mini-Reviews in Medicinal Chemistry Antioxidative Effects of Rhodiola Genus: Phytochemistry and Pharmacological Mechanisms against the Diseases
Current Topics in Medicinal Chemistry Sialic Acid and the Central Nervous System: Perspectives on Biological Functions, Detection, Imaging Methods and Manipulation
CNS & Neurological Disorders - Drug Targets Methods for Identifying Cardiovascular Agents: A Review
Recent Patents on Cardiovascular Drug Discovery Molecular Mechanisms of Thiamine Utilization.
Current Molecular Medicine The Association of MME microRNA Binding Site Polymorphism with the Risk of Late Onset Alzheimer’s Disease in Northern Han Chinese
Current Neurovascular Research