CX-614 is anampakine drug developed by Cortex Pharmaceuticals. It has been investigated for its effect onAMPA receptors.[1]
Chronic CX-614 treatments produce rapid increases in the synthesis of the brain-derived neurotrophic factorBDNF which has very important effects onsynaptic plasticity[2] and may have applications in the treatment of neurodegenerative diseases such as Alzheimer's disease.
Acute CX-614 treatments activatelocal mRNA translation (new protein synthesis) withindendrites[3] and this is mediated by a fast upregulation ofBDNF release. CX-614-dependent release of BDNF rapidly increases translation of proteins that are important for synaptic plasticity such asARC/Arg3.1 andCaMKIIalpha.[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 ofAMPA receptors with prolonged CX-614 administration can be avoided by designing and using short and intermittent treatment protocols, which could still upregulateBDNF protein levels without reducing the levels ofAMPA receptors.[8]
Importantly, such short and intermittent treatment protocols are neuroprotective againstneurotoxicity induced withMPTP 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 forParkinson's disease andAlzheimer'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.
^Hess US, Whalen SP, Sandoval LM, Lynch G, Gall CM (2003). "Ampakines reduce methamphetamine-driven rotation and activate neocortex in a regionally selective fashion".Neuroscience.121 (2):509–21.doi:10.1016/S0306-4522(03)00423-8.PMID14522010.S2CID23287000.
