Abstract
Depression is a major health issue, which is routinely treated with selective serotonin reuptake inhibitors. However, although these agents display a favorable effect on mood, they often fail to improve conditions that accompany depression including cognitive impairment and fatigue. In pre-clinical studies histamine H3 receptor antagonists have demonstrated both pro-cognitive and wake-promoting effects suggesting that the combination of a histamine H3 receptor antagonist and a serotonin reuptake inhibitor may have utility as an antidepressant therapy. To this end we sought to introduce histamine H3 receptor antagonist activity into both known selective serotonin reuptake inhibitors and novel templates. These efforts have afforded several series of compounds with the desired activities. Selected examples demonstrated in vivo efficacy both in pre-clinical models of depression and wakefulness.
Keywords: Histamine, histamine H3 receptor, histamine H3 receptor antagonists, serotonin, serotonin transporter (SERT), norepinephrine transporter (NET), dopamine transporter (DAT), selective serotonin reuptake inhibitors (SSRIs), depression, wakefulness
Current Topics in Medicinal Chemistry
Title: Exploration of Structure-Activity Relationships for Dual Serotonin Transporter Reuptake Inhibitors-Histamine H3 Receptor Antagonists
Volume: 10 Issue: 5
Author(s): Emily M. Stocking, Michael A. Letavic, Pascal Bonaventure and Nicholas I. Carruthers
Affiliation:
Keywords: Histamine, histamine H3 receptor, histamine H3 receptor antagonists, serotonin, serotonin transporter (SERT), norepinephrine transporter (NET), dopamine transporter (DAT), selective serotonin reuptake inhibitors (SSRIs), depression, wakefulness
Abstract: Depression is a major health issue, which is routinely treated with selective serotonin reuptake inhibitors. However, although these agents display a favorable effect on mood, they often fail to improve conditions that accompany depression including cognitive impairment and fatigue. In pre-clinical studies histamine H3 receptor antagonists have demonstrated both pro-cognitive and wake-promoting effects suggesting that the combination of a histamine H3 receptor antagonist and a serotonin reuptake inhibitor may have utility as an antidepressant therapy. To this end we sought to introduce histamine H3 receptor antagonist activity into both known selective serotonin reuptake inhibitors and novel templates. These efforts have afforded several series of compounds with the desired activities. Selected examples demonstrated in vivo efficacy both in pre-clinical models of depression and wakefulness.
Export Options
About this article
Cite this article as:
Stocking Emily M., Letavic Michael A., Bonaventure Pascal and Carruthers Nicholas I., Exploration of Structure-Activity Relationships for Dual Serotonin Transporter Reuptake Inhibitors-Histamine H3 Receptor Antagonists, Current Topics in Medicinal Chemistry 2010; 10 (5) . https://dx.doi.org/10.2174/156802610791111515
DOI https://dx.doi.org/10.2174/156802610791111515 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
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
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
History Repeats Itself: Pharmacodynamic Trends in the Treatment of Anxiety Disorders
Current Pharmaceutical Design Detecting Non-cognitive Features of Prodromal Neurodegenerative Diseases
Current Aging Science The Impact of Comorbid Diabetes Type 2 on Quality of Life in Cancer Patients Undergoing Chemotherapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Boosting Interleukin-10 Production: Therapeutic Effects and Mechanisms
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Heme Oxygenase Overexpression Attenuates Glucose-Mediated Oxidative Stress in Quiescent Cell Phase: Linking Heme to Hyperglycemia Complications
Current Neurovascular Research High Content Screening for G Protein-Coupled Receptors Using Cell-Based Protein Translocation Assays
Combinatorial Chemistry & High Throughput Screening Peripheral Mononuclear Cell Rejuvenation for Senescence Surveillance in Alzheimer Disease
Current Pharmaceutical Design Editorial: Big Data and New Drug Discovery: Tackling “Big Data” for Virtual Screening of Large Compound Databases
Current Computer-Aided Drug Design Proline-Rich Peptides: Multifunctional Bioactive Molecules as New Potential Therapeutic Drugs
Current Protein & Peptide Science All for Statins and Statins for All; An Update
Current Pharmaceutical Design From Surface to Nuclear Receptors: The Endocannabinoid Family Extends its Assets
Current Medicinal Chemistry Chemoprevention with Phytonutrients and Microalgae Products in Chronic Inflammation and Colon Cancer
Current Pharmaceutical Design Drug Therapy for Patients with Eating Disorders
Current Drug Targets - CNS & Neurological Disorders Editorial [ Smoking and Drinking Go Hand in Hand ]
Current Drug Abuse Reviews Genetic Variation Underlying Psychosis-inducing Effects of Cannabis: Critical Review and Future Directions
Current Pharmaceutical Design Advances in Extracorporeal Detoxification by MARS Dialysis in Patients with Liver Failure
Current Medicinal Chemistry Proteomics Approaches to Understand Linkage Between Alzheimer’s Disease and Type 2 Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets Inflammation Fueling Atrial Fibrillation Substrate: Seeking Ways to "Cool" the Heart
Medicinal Chemistry Predicting Dopamine Receptors Binding Affinity of N-[4-(4-Arylpiperazin- 1-yl) butyl]Aryl Carboxamides: Computational Approach Using Topological Descriptors
Current Drug Discovery Technologies Chemistry and Health Effects of Bioactive Compounds in Selected Culinary Aromatic Herbs
Current Nutrition & Food Science