50 years of hurdles and hope in anxiolytic drug discovery.
Guy Griebel,Andrew Holmes +1 more
TLDR
The major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (γ-aminobutyric acid)–benzodiazepine system are analyzed, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems.Abstract:
Anxiety disorders are the most prevalent group of psychiatric diseases, and have high personal and societal costs. The search for novel pharmacological treatments for these conditions is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. A huge volume of data has been generated by anxiolytic drug discovery studies, which has led to the progression of numerous new molecules into clinical trials. However, the clinical outcome of these efforts has been disappointing, as promising results with novel agents in rodent studies have very rarely translated into effectiveness in humans. Here, we analyse the major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (γ-aminobutyric acid)-benzodiazepine system, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems. We highlight various key issues that may have hampered progress in the field, and offer recommendations for how anxiolytic drug discovery can be more effective in the future.read more
Citations
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Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework.
Joseph E. LeDoux,Daniel S. Pine +1 more
TL;DR: It is argued that failure to recognize and consistently emphasize a distinction between circuits underlying two classes of responses elicited by threats has impeded progress in understanding fear and anxiety disorders and hindered attempts to develop more effective pharmaceutical and psychological treatments.
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Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders.
TL;DR: The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery.
Journal ArticleDOI
Contributions of the Central Extended Amygdala to Fear and Anxiety.
TL;DR: Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat and compel a reconsideration of the central extended amygdala's contributions toFear and anxiety and its role in neuropsychiatric disease.
Journal ArticleDOI
The developing utility of zebrafish models of neurological and neuropsychiatric disorders: A critical review.
TL;DR: Zebrafish have become a powerful tool in neuroscience research due to their genetic tractability, molecular/physiological conservation, small body size, ease of experimental manipulations in vivo, and rich behavioral repertoire.
Journal ArticleDOI
Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons.
Kalil Alves de Lima,Kalil Alves de Lima,Justin Rustenhoven,Justin Rustenhoven,Sandro Da Mesquita,Morgan Wall,Andrea Francesca Salvador,Andrea Francesca Salvador,Igor Smirnov,Igor Smirnov,Guilherme Cesar Martelossi Cebinelli,Guilherme Cesar Martelossi Cebinelli,Tornike Mamuladze,Tornike Mamuladze,Wendy Baker,Zach Papadopoulos,Zach Papadopoulos,Maria Beatriz Lopes,William Sam Cao,Xinmin Xie,Jasmin Herz,Jasmin Herz,Jonathan Kipnis,Jonathan Kipnis +23 more
TL;DR: A population of meningeal γδ17 T cells are characterized that use IL-17a to elicit anxiety-like behavior through cortical glutamatergic neurons, suggesting an evolutionary bridge between this conserved anti-pathogen molecule and survival behavioral traits in vertebrates.
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