Given the role of impaired regulation of glutamatergic neurotransmission in the pathophysiology of MADI and the long-term modulation of synaptic function induced by traditional antidepressants, growing interest addressed the development of drugs directly targeted on the glutamatergic system. As a global-leading company focusing on psychotropic drug development, Creative Biolabs has invested a lot of manpower, material resources, and financial resources in glutamate receptor regulators research in psychiatric disorders. With years of accumulation, we are capable of providing global researchers with high-quality target development services.
Introduction to Glutamate in Psychiatric Disorders
Glutamate neurotransmission dysfunction is increasingly considered a core feature of stress-related mental illnesses. For over half a century, the conceptual framework of research on these disorders has been dominated by the monoamine hypothesis, on which most of the drugs developed for clinical therapy are based. Although it was not acknowledged as a neurotransmitter until the early 1980s, glutamate has been recognized as the major excitatory neurotransmitter in the brain, with glutamatergic neurons representing about 80% of total neurons in the neocortex. In the past decade, it has become increasingly acknowledged that maladaptive changes in the structure and function of excitatory/inhibitory circuitry (representing the vast majority of neurons and synapses in the brain) have a primary role in the pathophysiology of mood and anxiety disorders (MADI), particularly major depression.
Glutamate Receptor Regulators and Psychiatric Disorders
Glutamate released in the synaptic cleft can bind ionotropic postsynaptic glutamate receptors, including AMPAR, N-methyl-D-aspartate receptor (NMDAR), and kainate receptors, or metabotropic glutamate receptors (mGluRs), localized at both presynaptic and postsynaptic sites. Several studies have consistently shown that chronic antidepressants selectively regulate glutamate receptor expression and function.
A number of recent, exciting studies reported rapid antidepressant action, both in preclinical and clinical studies, of low doses of high-affinity non-competitive NMDAR antagonists (particularly the dissociative anesthetic ketamine). It has been shown that a single subanesthetic dose of ketamine induces rapid (within hours) and sustained (up to 1 week) antidepressant efficacy in treatment-resistant patients, although the actual response to ketamine might be longer. These findings, particularly robustness, rapidity, and durability of the antidepressant effect, were unanticipated. Ketamine appears to target directly the core depressive symptoms such as sad mood, suicidality, and helplessness, rather than inducing a nonspecific mood-elevating effect.
The anxiolytic agent fenobam is a potent antagonist of the mGlu5 subtype of metabotropic glutamate receptor. Fenobam was previously shown to have clinical efficacy as an antianxiety agent but had an unknown mechanism of action, a finding consistent with a growing body of literature showing that mGluR5 blockade is anxiolytic.
It has been reported that mGlu2/3 antagonists may increase synaptic levels of glutamate, and potentiate AMPAR-mediated transmission and firing rates of serotonin and dopamine neurons, thereby increasing extracellular levels of monoamines. Moreover, it was shown that, as for ketamine, the behavioral effects of selective mGlu2/3 antagonists are dependent on the mammalian target of rapamycin signaling.
Evidence of combined dysfunction of the dopamine and glutamate neurotransmitter systems (and particularly hypofunction of the NMDA receptor) appears to be an important mechanism in schizophrenia. Thus, there has been much interest in targeting the modulation of NMDA receptor function by increasing the availability of glycine within the synaptic cleft. Clinical studies with novel glycine reuptake inhibitors will provide critical information regarding the validity of this therapeutic concept for the treatment of schizophrenia and other disorders associated with NMDA receptor hypofunction.
It has been reported that MAP kinase II was uniquely affected in the hippocampus by the repeated MK-801 treatment. Evidence exists for a functional role of some of these in learning and memory.
Services at Creative Biolabs
As an industry-leading CRO company, Creative Biolabs has been focusing on drug development for years and thus accumulated extensive professional experience as well as established a comprehensive drug development system. With excellent experts specialized in psychotropic and advanced technology, we are capable of providing global researchers with a top-rated customer experience. Our scope of services cover every step of the target development of the psychiatric disorder.
Advantages
-
Worry-free one-stop services
-
Reliability and information security
-
Professional expert team
-
High efficiency and cost-efficient
Glutamate receptor regulators are extensively studied and have potentially been applied to psychiatric disorders. Based on an advanced technology platform, Ph.D. level scientists, and extensive industrial experience, Creative Biolabs provides high-quality services to meet global customers' specific requirements. If you have any other questions, please feel free to contact us.
For Research Use Only.
