CX717

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CX717 is an ampakine compound created by Christopher Marrs and Gary Rogers in 1996[1] at Cortex Pharmaceuticals. It affects the neurotransmitter glutamate, with early trials showing the drug improves cognitive functioning and memory.

Contents

[edit] Approval process

In 2005 The U.S. Food and Drug Administration (FDA) accepted Cortex Pharmaceuticals' IND (Investigational New Drug) application to initiate pilot Phase II clinical trials in the United States.

Also, in 2005, the United States Department of Defense funded a study to look into CX717 and the physiological effects of sleepiness. The study found that rhesus monkeys performed faster and better after receiving the drug, and it counteracted the effects of sleep deprivation.

However, a 2006 study funded by DARPA found that CX717 did not improve cognitive performance in humans subjected to simulated night shift work. [2]

April 18 2007 Cortex Pharmaceuticals submitted two large data packages to the FDA regarding CX717. One data set went to the FDA's Division of Neurology Drug Products for the treatment of Alzheimer's disease, while the other went to the Division of Psychiatry Products where the company intends to file a second CX717 IND for the treatment of ADHD. The submitted data package provides clear evidence that the specific histopathological changes seen in animal toxicology studies, which previously caused the FDA to put CX717 on clinical hold, is a postmortem fixation artifact and is not found in the tissue of the animal when it is still living.

Roger G. Stoll, Ph.D., Chief Executive Officer of Cortex, stated,

“When CX717 was removed from clinical hold on October 6, 2006 by the Neurology Division a dose was permitted for continuing a study in patients with Alzheimer's disease, but that dose was too low to permit the assessment of the drug in patients with ADHD. Further information was needed to better understand the cause of the histopathological changes. We now have a substantial data base which clearly documents the fact that the histological changes of concern occur postmortem when the fixative solution is used to prepare the slides of the tissue specimens.”

In early March 2006 Cortex reported in a small pilot Phase II study, that CX717 had demonstrated positive clinical and statistical results on the primary endpoint, the ADHD rating scale and the sub-scales related to attention and hyperactivity which are used for the approval of all currently available ADHD treatments. Consistent with all previous studies involving over 220 patients and healthy adults, this study demonstrated that CX717 was safe, well tolerated, and produced no increase in heart rate, blood pressure or other cardiovascular side effects.

However, in October 2007 the FDA denied Cortex's IND application for a Phase IIb study of CX717 for treatment of ADHD, based on the same animal toxicology results. Cortex responded by inactivating the application, although it will "continue its plans to develop CX717 for the acute treatment of respiratory depression (RD) and continue its study of CX717 in its Alzheimer’s disease PET scan study. Cortex believes that the IND application previously filed with the Division of Neurology Products of the FDA for the treatment of Alzheimer’s disease will not be affected by the actions of the DPP."[3] The company hopes that after the use of the compound in treating a high-risk acute condition is approved and well-established, the risks of longer-term use at higher doses, such as for treatment of ADHD, will be shown to be less than the FDA had concluded.

[edit] Related AMPAkines

Other AMPAkine drugs from Cortex Pharmaceuticals such as CX614 have already been researched for use in treating Alzheimer's disease and ADHD. These drugs were reasonably effective at reducing the symptoms of Alzheimer's and it is hoped that they will also slow the progression of the disease. CX717 is a newer drug in the same series. The chemical structure of CX717 has not yet been revealed by Cortex Pharmaceuticals, but is presumably similar to earlier compounds in the series as shown below. It is very unusual for research on a compound to be released in scientific journals without disclosing exactly what the compound consists of, but this information is likely to have been kept confidential for reasons of intellectual property, and also because the research on CX717 was partially funded by DARPA, the United States Defense Advanced Research Projects Agency.

Cortex Pharmaceutical AMPAkines

[edit] References

  1. ^ Benzofurazan compounds for enhancing glutamatergic synaptic responses. Retrieved on 2008-4-04.
  2. ^ Cortex News & Events. Retrieved on 2007-10-21.
  3. ^ FDA’s Psychiatric Division has Rejected Cortex’s Request to Study CX717 in Phase IIb ADHD Study. Retrieved on 2008-02-28.
  • Bast T, da Silva BM, Morris RG (2005). "Distinct contributions of hippocampal NMDA and AMPA receptors to encoding and retrieval of one-trial place memory". J. Neurosci. 25 (25): 5845–56. doi:10.1523/JNEUROSCI.0698-05.2005. PMID 15976073. 
  • Porrino LJ, Daunais JB, Rogers GA, Hampson RE, Deadwyler SA (2005). "Facilitation of task performance and removal of the effects of sleep deprivation by an ampakine (CX717) in nonhuman primates". PLoS Biol. 3 (9): e299. doi:10.1371/journal.pbio.0030299. PMID 16104830. 
  • [1] Cortex Pharmaceuticals press release

[edit] See also

v • d • e
Psychoanaleptics: psychostimulants, agents used for ADHD and nootropics (N06B)
Centrally acting sympathomimetics
Xanthine derivatives
Racetams
Ampakines
Eugeroics
Histamine H3 receptor antagonists
Other psychostimulants and nootropics
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