What Are the Properties of CX717?
CX717 is a compound discovered by Cortex Pharmaceuticals in 1996.
CX717 modulates the glutamatergic system in the brain by interacting with the glutamate receptor AMPA. Hence, CX717 is an ampakine. By acting on the glutamate system, CX717 strengthens synaptic connections. It possess cognitive enhancing properties in animal models, but more research is needed in humans.
How Does CX717 Strengthen Synapses?
CX717 strengthens the synapses between neurons by promoting a neurophysiological process known as Long-Term Potentiation (LTP). Specifically, CX717 enhances LTP by:
- Directly acting upon AMPA Receptors and activating them 1
- Indirectly, by enhancing NMDA Receptor activity (another glutamate receptor) by removing magnesium block of NMDA 2 (via AMPA activation)
CX717 is still under clinical investigations and as a result, the exact dosage regime is not known. However, in clinical studies doses range between 200mg-1000mg per day.
Is CXC717 an Effective Cognitive Enhancer?
There are a series of both preclinical and clinical evidence suggesting that Ampakines, in general, have beneficial effects upon cognition. Specifically,
- Ampakines have been linked with a cumulative enhancement of performance in a spatial short-term memory task in rats3
- Neurobiological studies have shown that Ampakines produce a threefold alteration in the encoding and organization of information in normal brains overall enhancing cognition 4
- In healthy elderly volunteers, Ampakines produced a significant enhancement in memory performance in assigned tasked5.
- In healthy young volunteers, Ampakines have been linked with improved of most aspects of memory (except for task requiring cued recall) 6.
In general, CX717 has shown to produce beneficial effects on cognition:
- In non-human Primates, CX717 has been shown to indeed enhance cognition by promoting the activity of hippocampal cells in the brain 7
- In humans, CX717(1000mg/day) has been linked to improvement in attention-based task performance 8
However, researchers have also reported negative findings:
- In rats, CX717 was linked to detrimental effects in object recognition memory tasks 9
- In humans, a range of doses was not effective at reversing performance and alertness deficits associated with night work shifts 10.
Possible Uses for CXC717: Beyond Cognitive Enhancement
Ampakines have been suggested for use, not only for cognitive enhancement in healthy individuals but also for the treatment of the following medical conditions:
- Schizophrenia: Clinical studies have shown that Ampakines significantly boost the antipsychotic properties of clozapine11; moreover Ampakines correct the behavior of animal models of schizophrenia12
- Clinical Depression: In animal models of depression Ampakines have been linked with mood enhancing properties12
- Rett’s Syndrome: In animal models of Rett Syndrome Ampakines have the ability to restore abnormal breathing frequency associated with this genetic condition13
- Alzheimer’s disease: Due to the ability of Ampakines to significantly improve short-term memory and task performance memory it has been suggested for use in Alzheimer's disease 14.
- Huntington’s Disease: Chronic treatment with Ampakines have been linked to profound improvement in cognitive difficulties associated with early stages of Huntington's disease15
- Angelmans’s Disease: Ampakines may have a crucial role in the treatment of Angelmans’s disease since they reverse associated neuron structural abnormalities ultimately enhancing LTP and preventing learning impairments16
- Autism: In autism, Ampakines have been linked to marked improvement in social cognition promoting sociability in animal models of autism 17.
CX717 and the Military
Ampakines are under clinical investigation by the US military army as:
- Cognitive enhancers and alertness promoters for soldiers in high-stress extended combat situations18
- Neuroprotective agents against neurotoxic insults12
Is CX717 dosing Safe?
CX717 is well tolerated by most people; it is linked to a small number of adverse effects which are:
Consequences of Long-Term CX717 Use
Ampakines due to their innate ability to enhance glutamate signaling chronic use can potentially be associated with the following worrisome adverse events:
- Excitotoxicity19: A process by which nerve cells are damaged/killed due to excess stimulation by glutamate
- Poor Emotional Regulation and Impaired Behavioural Inhibition19: Due to excess synapse formation in the brain regions controlling the processes of emotional and affective functions.
- Development of autistic traits (in teens, adolescents, and young adults)19:Sustained heightened synapse activity can lead to reduced normal developmental synaptic elimination (known as synaptic pruning; reduced synaptic pruning has been linked to the development of autistic traits.
- Impairments in Spatial Memory and Motor function19. By enhancing LTP Ampakines decrease another neurophysiological process known as long-term Depression (LTD); this process is crucial for spatial recognition and motor function.
Should I Use CX717?
Ampakines are a class of cognitive enhancers that may be of benefit not only as nootropics but also for the treatment of various neurological and psychiatric diseases. While promising agents, very little is known about their overall physiological effects and have been linked with significant dangers.
CX717 is only of its kind to reach phase 1 clinical studies for the treatment of Alzheimer’s disease as it showed great benefits in animal studies. However, CX-717 approval was halted as it was linked to marked brain tissue damage in animal and the FDA concluded that it required further animal testing before it can be assessed in humans20.
Overall due to so little evidence concerning its effectiveness and safety in humans, it is advised that CX-717 (and as an extension Ampakines) should not be taken recreationally as cognitive enhancers. Moreover, under no circumstances should they be given to healthy children, teens and young adults as they are very prone to developing autistic traits that occur as a result of sustained enhanced synapse activity.
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Lu, W., Man, H., Ju, W., Trimble, W. S., MacDonald, J. F., and Wang, Y. T. (2001). Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. Neuron 29, 243– 254. doi: 10.1016/s0896-6273(01)00194-5 ↩
Hampson RE1, Rogers G, Lynch G, Deadwyler SA.Facilitative effects of the ampakine CX516 on short-term memory in rats: enhancement of delayed-nonmatch-to-sample performance. J Neurosci. 1998 Apr 1;18(7):2740-7. ↩
Lynch G1, Gall CMAmpakines and the threefold path to cognitive enhancement. Trends Neurosci. 2006 Oct;29(10):554-62 ↩
Wezenberg E1, Verkes RJ, Ruigt GS, Hulstijn W, Sabbe BG. Acute effects of the ampakine farampator on memory and information processing in healthy elderly volunteers. Neuropsychopharmacology. 2007 Jun;32(6):1272-83. ↩
Ingvar M1, Ambros-Ingerson J, Davis M, Granger R, Kessler M, Rogers GA, Schehr RS, Lynch G.Enhancement by an ampakine of memory encoding in humans. Exp Neurol. 1997 Aug;146(2):553-9. ↩
Hampson RE1, España RA, Rogers GA, Porrino LJ, Deadwyler SA. Mechanisms underlying cognitive enhancement and reversal of cognitive deficits in nonhuman primates by the ampakine CX717. Psychopharmacology (Berl). 2009 Jan;202(1-3):355-69. ↩
Boyle J1, Stanley N, James LM, Wright N, Johnsen S, Arbon EL, Dijk DJ.Acute sleep deprivation: the effects of the AMPAKINE compound CX717 on human cognitive performance, alertness and recovery sleep. J Psychopharmacol. 2012 Aug;26(8):1047-57. ↩
Zheng Y1, Balabhadrapatruni S, Masumura C, Darlington CL, Smith PF. Effects of the putative cognitive-enhancing ampakine, CX717, on attention and object recognition memory. Curr Alzheimer Res. 2011 Dec;8(8):876-82 ↩
Wesensten NJ1, Reichardt RM, Balkin TJ. Ampakine (CX717) effects on performance and alertness during simulated night shift work. Aviat Space Environ Med. 2007 Oct;78(10):937-43. ↩
Goff, D. C., Leahy, L., Berman, I., Posever, T., Herz, L., Leon, A. C., et al. (2001). A placebo-controlled pilot study of the ampakine CX516 added to clozapine in schizophrenia. J. Clin. Psychopharmacol. 21, 484–487. doi: 10.1097/00004714- 200110000-00005 ↩
Arai, A. C., and Kessler, M. (2007). Pharmacology of ampakine modulators: from AMPA receptors to synapses and behavior. Curr. Drug Targets 8, 583–602. ↩
 Ogier, M., Wang, H., Hong, E., Wang, Q., Greenberg, M. E., and Katz, D. M. (2007). Brain-derived neurotrophic factor expression and respiratory function improve after ampakine treatment in a mouse model of Rett syndrome. J. Neurosci. 27, 10912–10917\.
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Simmons, D. A., Rex, C. S., Palmer, L., Pandyarajan, V., Fedulov, V., Gall, C. M., et al. (2009). Up-regulating BDNF with an ampakine rescues synaptic plasticity and memory in Huntington’s disease knockin mice. Proc. Natl. Acad. Sci. U S A 106, 4906–4911. ↩
Baudry, M., Kramar, E., Xu, X., Zadran, H., Moreno, S., Lynch, G., et al. (2012). Ampakines promote spine actin polymerization, long-term potentiation and learning in a mouse model of Angelman syndrome. Neurobiol. Dis. 47, 210–215. ↩
Silverman, J. L., Oliver, C. F., Karras, M. N., Gastrell, P. T., and Crawley, J. N. (2013). AMPAKINE enhancement of social interaction in the BTBR mouse model of autism. Neuropharmacology 64, 268–282. ↩
Saletan, W. (2008). Night of the living meds: the US military’s sleep-reduction program, slate magazine. The Slate Group. Accessed 11-1-2013. http:// www.slate.com/articles/healthandscience/humannature/2008/07/nightof_ thelivingmeds.html ↩
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