CX-614 is an

ampakine Ampakines, also stylized as AMPAkines, are a subgroup of AMPA receptor positive allosteric modulators with a benzamide or closely related chemical structure. They are also known as "CX compounds". Ampakines take their name from the AMPA recepto ...

drug developed by Cortex Pharmaceuticals. It has been investigated for its effect on

AMPA receptor The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the ce ...

s. Chronic CX-614 treatments produce rapid increases in the synthesis of the brain-derived neurotrophic factor

BDNF Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canon ...

which has very important effects on

synaptic plasticity In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circui ...

and may have applications in the treatment of neurodegenerative diseases such as Alzheimer's disease. Acute CX-614 treatments activate local mRNA translation (new protein synthesis) within

dendrites Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the ...

and this is mediated by a fast upregulation of

release. CX-614-dependent release of BDNF rapidly increases translation of proteins that are important for synaptic plasticity such as ARC/Arg3.1 and CaMKIIalpha. CX-614 has also been proposed as a treatment for conditions such as depression and schizophrenia, but produces receptor downregulation following chronic administration, which might limit the potential for extended use. However, downregulation of

AMPA receptors The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the centr ...

with prolonged CX-614 administration can be avoided by designing and using short and intermittent treatment protocols, which could still upregulate

protein levels without reducing the levels of

. Importantly, such short and intermittent treatment protocols are neuroprotective against neurotoxicity induced with

MPTP MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study d ...

and MPP⁺ in cultured midbrain (mesencephalic) and hippocampal organotypic slices. These results uncovered the neuroprotective effects of CX-614 and indicated that opened the way for further experimentation with CX-614 as an important new treatment for

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

and Alzheimer's disease. CX-614 has also been shown to reduce the behavioural effects of methamphetamine in mice, and may have application in the treatment of stimulant abuse.

References

{{Ionotropic glutamate receptor modulators Pyrrolidines Ampakines Lactams Benzodioxoles AMPA receptor positive allosteric modulators Experimental drugs

See also

References