![conference banner](/images/conference-banner.jpeg)
Abstract
For more than four decades there has been a search for selective inhibitors of GABA transporters. This has led to potent and selective inhibitors of the cloned GABA transporter subtype GAT1, which is responsible for a majority of neuronal GABA transport. The only clinically approved compound with this mechanism of action is Tiagabine. Other GABA transporter subtypes have not been targeted with comparable selectivity and potency. We here review a comprehensive series of competitive inhibitors that provide information about the GABA recognition site and summarise the structure-activity relations in a ligand-based pharmacophore model that suggests how future compounds could be designed. Finally, some of the recent results on subtype-characterised competitive inhibitors and recent lipophilic aromatic GABA uptake inhibitors are reviewed.
Keywords: Acyclic GABA Analogues, THPO, Nipecotic Acid, Aminocyclohexanecarboxylic Acid (ACHC), GABA uptake assay
Current Topics in Medicinal Chemistry
Title: Structure-Activity Relationships of Selective GABA Uptake Inhibitors
Volume: 6 Issue: 17
Author(s): Signe Hog, Jeremy R. Greenwood, Karsten B. Madsen, Orla M. Larsson, Bente Frolund, Arne Schousboe, Povl Krogsgaard-Larsen and Rasmus P. Clausen
Affiliation:
Keywords: Acyclic GABA Analogues, THPO, Nipecotic Acid, Aminocyclohexanecarboxylic Acid (ACHC), GABA uptake assay
Abstract: For more than four decades there has been a search for selective inhibitors of GABA transporters. This has led to potent and selective inhibitors of the cloned GABA transporter subtype GAT1, which is responsible for a majority of neuronal GABA transport. The only clinically approved compound with this mechanism of action is Tiagabine. Other GABA transporter subtypes have not been targeted with comparable selectivity and potency. We here review a comprehensive series of competitive inhibitors that provide information about the GABA recognition site and summarise the structure-activity relations in a ligand-based pharmacophore model that suggests how future compounds could be designed. Finally, some of the recent results on subtype-characterised competitive inhibitors and recent lipophilic aromatic GABA uptake inhibitors are reviewed.
Export Options
About this article
Cite this article as:
Hog Signe, Greenwood R. Jeremy, Madsen B. Karsten, Larsson M. Orla, Frolund Bente, Schousboe Arne, Krogsgaard-Larsen Povl and Clausen P. Rasmus, Structure-Activity Relationships of Selective GABA Uptake Inhibitors, Current Topics in Medicinal Chemistry 2006; 6 (17) . https://dx.doi.org/10.2174/156802606778249801
DOI https://dx.doi.org/10.2174/156802606778249801 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Probiotics/Prebiotics in Viral Respiratory Infections: Implication for Emerging Pathogens
Recent Patents on Biotechnology Nonnucleoside Inhibitors of Adenosine Kinase
Current Pharmaceutical Design Recent Advances in Antiepileptic Herbal Medicine
Current Neuropharmacology Antiepileptic Drugs Based on the α-Substituted Amide Group Pharmacophore: From Chemical Crystallography to Molecular Pharmaceutics
Current Pharmaceutical Design Modulation of GABAA Receptors in the Treatment of Epilepsy
Current Pharmaceutical Design Biophysical Modeling and Associated Signal Modeling in Functional Magnetic Resonance Imaging
Neuroscience and Biomedical Engineering (Discontinued) Decreased Expression of Sox-1 in Cerebellum of Rat with Generalized Seizures Induced by Kindling Model
CNS & Neurological Disorders - Drug Targets Pharmacological Manipulation of Neural Progenitor Pathways In Situ: Possibilities for Neural Restoration in the Injured Adult Brain
Current Medicinal Chemistry - Central Nervous System Agents Chronic Stress Impacts on Olfactory System
CNS & Neurological Disorders - Drug Targets Non-Celiac Gluten Sensitivity Triggers Gut Dysbiosis, Neuroinflammation, Gut-Brain Axis Dysfunction, and Vulnerability for Dementia
CNS & Neurological Disorders - Drug Targets Changes in Psychiatric Diagnoses During the Transition Phase from Childhood to Adulthood in a Group of Patients with Intellectual Disability
Adolescent Psychiatry Tactile Angle Discrimination Decreases due to Subjective Cognitive Decline in Alzheimer’s Disease
Current Alzheimer Research Neuroprotective Effects of Drug-Induced Therapeutic Hypothermia in Central Nervous System Diseases
Current Drug Targets Editorial (Thematic Issue: In vivo MRS: Techniques and Applications)
Current Molecular Imaging (Discontinued) Meet Our Editorial Board Member
Current Aging Science P2X7 Receptors: Channels, Pores and More
CNS & Neurological Disorders - Drug Targets Involvement of Membrane Channels in Autoimmune Disorders
Current Pharmaceutical Design Therapeutic Potential of Voltage Gated Calcium Channels
Mini-Reviews in Medicinal Chemistry Neural Stem Cell Niches in Health and Diseases
Current Pharmaceutical Design Oxytocin Effect in Adult Patients with Autism: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
CNS & Neurological Disorders - Drug Targets