Drug targets for cognitive enhancement in neuropsychiatric disorders.
Open accessAbstract
The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA(A) α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.
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- Authors
- Wallace, T. L., Ballard, T. M., Pouzet, B., Riedel, W. J., & Wettstein, J. G.
- Affiliations
- SRI International (US)
- F. Hoffmann-La Roche AG (CH)
- Corresponding author
- Wettstein, Joseph G.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 99
- Issue
- 2
- Pages
- 130-145
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2123713110
- Cited by
- 127
- References
- 253
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 3 · 2016: 12 · 2015: 11 · 2014: 18 · 2013: 17 · 2012: 25
- FWCI
- 1.92
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- cognitive enhancement, therapeutic target, cognitive impairment, Alzheimer's disease, schizophrenia, attention deficit hyperactivity disorder, cholinergic receptors, nicotinic agonists, serotonergic agonists, histamine H3 receptor antagonists, phosphodiesterase, long-term memory, working memory, Down syndrome, preclinical model selection, cognitive assessment battery
- MeSH terms
- Animals, Cognition Disorders, Humans, Learning, Memory, Phosphodiesterase Inhibitors, Receptors, Cholinergic, Receptors, Dopamine, Receptors, Histamine, Receptors, Serotonin, Receptors, Glutamate, Receptors, GABA, Nootropic Agents, Glycine Plasma Membrane Transport Proteins
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