NMDA Modulation for CNS Disorders
A New Perspective on Brain Function Modulation
SyneuRx believes that NMDA receptors are the grand regulator of the brain. Therefore, solutions to the current unmet needs in many central nervous system (CNS) disorders need to involve therapies that modulate NMDA receptor functions.
Glutamate is the most abundant neurotransmitter in the brain. Unlike dopamine and serotonin receptors that are restricted to well-defined pathways in limited parts of the brain, glutamate signaling occurs throughout the brain. In addition, it appears that glutamate can exert both facilitatory and inhibitory control over other neurotransmitters such as dopamine release. The complex glutamate system is controlled by three types of receptors, with NMDA receptors being the most important, complicated, and delicate ones. Thus, the NMDA system likely functions as the key control knob of the glutamate neurotransmission activities in the brain.
The NMDA system is known to play a central role in fundamental brain functions, including synaptic plasticity (important for learning and memory), formation of neural networks during brain development, and repair of the CNS. Abnormalities in the NMDA system are found to be associated with many psychiatric and neurological disorders, including schizophrenia, bipolar disorder, major depressive disorder, ADHD, and Alzheimer’s disorder.
SyneuRx is developing innovative NMDA modulators that carefully fine-tune the balance of NMDA functioning, as opposed to imposing overly excitatory or inhibitory controls over NMDA to reduce the chance of CNS dysfunction and disorders.
Three Mechanisms of Action
The NMDA system can be modulated by three mechanisms of actions:
(1) D-amino acid oxidase (DAAO) inhibitors
This group of compounds maintain or increase the cellular level of D-serine by inhibiting its degradation by DAAO. NaBen®, ClozaBen®, Tanquilynne® are DAAO inhibitors.
(2) Glycine transporter (GlyT-1) inhibitors
GlyT-1 inhibitors block glycine reuptake in order to build up synaptic glycine levels that can enhance the NMDA function. Synapsinae® is a GlyT-1 inhibitor.
(3) NMDA-glycine site modulator
Using full or partial agonist and/or antagonist to modulate the glycine level on the glycine site directly. Synxyrin® is a NMDA-glycine agonist as well as a partial antagonist.