CX-614

CX-614

CX-614 is an ampakine drug developed by Cortex Pharmaceuticals. It has been investigated for its effect on AMPA receptors.[1]

Chronic CX-614 treatments produce rapid increases in the synthesis of the brain-derived neurotrophic factor BDNF which has very important effects on synaptic plasticity [2] 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 [3] and this is mediated by a fast upregulation of BDNF 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.[3]

CX-614 has also been proposed as a treatment for conditions such as depression and schizophrenia,[4][5] but produces receptor downregulation following chronic administration, which might limit the potential for extended use.[6][7]

However, downregulation of AMPA receptors with prolonged CX-614 administration can be avoided by designing and using short and intermittent treatment protocols, which could still upregulate BDNF protein levels without reducing the levels of AMPA receptors.[8]

Importantly, such short and intermittent treatment protocols are neuroprotective against neurotoxicity induced with MPTP and MPP+ in cultured midbrain (mesencephalic) and hippocampal organotypic slices.[9]

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 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.[10]

References