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]
^Arai AC, Kessler M, Rogers G, Lynch G (2000). "Effects of the potent ampakine CX614 on hippocampal and recombinant AMPA receptors: interactions with cyclothiazide and GYKI 52466". Mol. Pharmacol. 58 (4): 802–13.
doi:
10.1124/mol.58.4.802.
PMID10999951.
S2CID6489143.
^Lauterborn JC, Truong GS, Baudry M, Bi X, Lynch G, Gall CM (Oct 2003). "Chronic elevation of brain-derived neurotrophic factor by ampakines". J Pharmacol Exp Ther. 307 (1): 297–305.
doi:
10.1124/jpet.103.053694.
PMID12893840.
S2CID1235935.