Ampakine CX1739? over the counter nootropics?

[JimC.]

While Adderall helps a lot, I confess I’d like to be a lab rat to try some of the newfangled things out there. The Neto1 results at Sick Kids a year ago still sticks in my mind. Any update on availability of ampakines; is it unwise to self-medicate with nootropics that some mail order and health food places have (racetam group i.e. Piracetam )?

“Additionally, a novel AMPAKINE molecule, CX1739, is currently in Phase I clinical trials and is targeted to begin Phase II clinical trials for ADHD in Q2 2009. Cortex Pharmaceuticals, Inc.

REPORT ABUSE

[Anonymous]

I am not aware of CX1739 coming to Canada or in the pipeline but I will investigate this.

I have done a search looking for Piracetam and ADHD and have not found any links. But your point about using this drug is very interesting. When I was a medical student, a thought this medication would be excellent in improving cognitive functioning as it was being looked at in Alzheimer’s disease at that time. That was 20 years ago and it got lost somewhere. Would I prescribe it for ADHD? No, not yet.

We need more study so I would be weary of this for now. I couldn’t even find any case reports which is odd because you would think someone must have experimented in a few patients or even a Letter to the Editor somewhere. If anyone finds information, I would certainly be interested.

REPORT ABUSE

[JimC.]

Cortex in the USA had CX!&#( turned down as an ADD drug by the regulator, and they decided to back off. Clinical Developments

from their site…see latter paragraphs…

Cortex has completed several Phase I human safety and tolerability studies with CX717 involving over 100 subjects, including elderly subjects, tested at doses up to 1600mg per day. The plasma half-life of CX717 was found to be 9-10 hours, and CX717 exhibited an excellent safety and tolerability profile. This was followed by the initiation of six Phase IIa studies, three of which have been completed. The first CX717 Phase IIa human study was in 16 subjects and evaluated three doses of CX717 (100mg, 300mg, 1000mg) and matching placebo in a double-blinded design in normal subjects that had been sleep deprived for 28 hours. CX717 was found to be safe and well tolerated by all subjects in the sleep deprivation study, and improved alertness with the 300mg and 1000mg doses. Some cognitive tests in this same study also provided early indications of positive responses. In all doses of CX717, there was evidence of cerebral arousal without systemic activation, e.g., no increases in blood pressure or heart rate, which are commonly seen with caffeine, amphetamines and other stimulants.

The second completed Phase IIa study was a 48-subject trial evaluating excessive daytime sleepiness in a shift work simulation supported and conducted by the Defense Advanced Research Projects Agency (DARPA). In this study, CX717 did not demonstrate a significant effect on cognitive performance, although EEG studies confirmed an effect on the sleep architecture, consistent with the first sleep deprivation study.

The third Phase IIa study enrolled 68 moderate to severe adult ADHD patients in a randomized, double-blind, placebo-controlled, two-way crossover design study performed at seven U.S. sites. The primary outcome measure was the ADHD Rating Scale (ADHD-RS) which evaluated both the inattentiveness and hyperactivity symptoms. The overall ADHD-RS score showed a statistically significant effect (p<0.002) in the 800mg twice-daily dose group, with patients demonstrating a statistically significant effect on both the hyperactivity (p=0.013) and inattentiveness subscale (p=0.031) as compared to placebo. CX717 was well tolerated, and there were no serious adverse events or other significant safety concerns with either dose. This data provides the first study demonstrating Proof-of-Concept in humans with an AMPAKINE compound for the treatment of adult patients with ADHD. The Company had planned to pursue a larger Phase IIb study in adult patients with ADHD because of the advantages over the current treatments shown below:

In March 2006, CX717 was put on clinical hold by the FDA’s Division of Neurology Drug Products due to a finding in a preclinical toxicology study. Further studies by Cortex suggested that the histopathology changes seen at very high doses of CX717 in preclinical toxicology studies were due to a post mortem artifact that occurs during the tissue fixation process. In October 2007, the Neurology Division of the FDA allowed Cortex to resume enrollment of the Phase IIa Alzheimer’s disease study. The design of this study is to assess two different CX717 doses in mild-to-moderate Alzheimer’s disease (AD), with each patient receiving psychometric tests and PET scans at different time intervals while on active drug or placebo. However, the FDA’s Division of Psychiatry Products did not give approval for a clinical study in adult patients with ADHD.

In May 2007, Cortex completed a Patent License Agreement with the University of Alberta, BC for the worldwide use of AMPAKINE compounds to reverse or prevent respiratory depression induced by therapeutic doses of opiate analgesic and sedative anesthetic agents, including barbiturates without the loss of the desired therapeutic; analgesia and sedation from these respective classes of drugs commonly utilized in the majority of surgical cases performed in both hospital settings and during out –patient surgical procedures. Based on data from the use of CX717 and other AMPAKINE compounds in several animal species, AMPAKINE compounds may be broad spectrum reversal agents for multiple classes of drugs that depress central nervous system activity and lead to respiratory depression events that can be life threatening. Milder forms of breathing cessation, such as central and obstructive sleep apneas could potentially constitute additional treatment targets for the Company to pursue.

REPORT ABUSE

[Anonymous]

Wow! with info like this, who needs me? Thanks for the detailed and very thoughtful answers.

REPORT ABUSE

[JimC.]

Update (I think) might be a setback, who knows… Cortex sold their rights for ampakine CX 717 to Biovail, who got swallowed by Valeant. The good news is that CX717 is in the pipeline, but I figure I’ll be dead by the time it gets to market.

http://www.valeant.com/products/pipeline/index.jsp

“Cortex retains all rights to the non-acquired AMPAKINE compounds for treatment of neurodegenerative diseases and psychiatric diseases which historically have been part of its portfolio. “As a result of this transaction, we will be in the position to continue the oral Phase IIa sleep apnea trial with CX1739 and to initiate a Phase II clinical trial for the treatment of ADHD very soon,” commented Mark A Varney. “Additionally, we are pushing ahead to develop the CX2007 and CX2076 series of compounds and move one of those analogs into the clinic as soon as possible.”

REPORT ABUSE

[Anonymous]

I’ve tried piracetam, aniracetam, and phenylpiracetam. All had some effect in helping with some aspects of ADD. It’s a really subtle and hard to describe effect mostly felt in areas of socialization and organizing my thoughts. While not necessarily making me super organized and purpose driven like ritalin and adderall, they seem to increase creativity and an ability to focus the creativity. The best way to put it is this, they help, the effects are subtle but an improvement as opposed to the heavy handedness of an amphetamine or methylphenidate.

I’ve recently ordered centrophenoxine and pramiracetam to see how I respond to these. I think so far aniracetam seems to be somewhat suited for ADD since it also seems to be an effective anxiolytic. Phenylpiracetam and noopept may also be beneficial for ADD. Since phenylpiracetam is so expensive, I didn’t play with the dosage too much. I haven’t tried noopept yet, but I would like to see how it helps me get rid of many aspects of my learned helplessness from growing up with ADD and a very emotionally abusive mother. Noopept has shown efficacy in treating rats with learned helplessness.

As far as AMPA, aniracetam has been shown to modulate AMPA receptors. I’m not aware of any research showing AMPA effects from the other racetams but wouldn’t be surprised if many of the racetams have activity there.

Finally, the cholinergics such as DMAE, CDP-choline, and Alpha-GPC have shown some efficacy in research and anecdotally in helping ADD alone. They are usually necessary with the racetams to prevent side effects from acetylcholine depletion I suppose. I believe AMPA, cholinergics, and racetams do hold a lot of potential for providing non-controlled substance way of treating ADD. However, the dosing and combination will be tricky from individual to individual.

REPORT ABUSE

[Anonymous]

Thank you for your insights. What is the target symptom (s) that you are hoping to improve within the domain of ADHD? Keep us posted in your progress.

REPORT ABUSE

[Anonymous]

That’s a good question.

After so many years of having ADHD and major depressive disorder, all kinds of other comorbid conditions have been added on. I’ve been experimenting with all kinds of approaches to all the problems I have and would like to fix. Sometimes when I am targeting a totally different problem, I get a new insight or experience a symptom of ADHD get better.

The main battleground does seem to be the dopamine system, but with the nootropics we are usually playing with acetylcholine. There also seems to be some benefit in NMDA antagonism which some of the nootropics address. For example, many of the people combating amphetamine tolerance issues have reported success in using magnesium, theanine, memantine, amantidine, and others. Acetyl L-Carnitine has been shown to increase NMDA recepters in experiments with one dose. Current research is also looking at using memantine and other NMDA antagonists in ADHD. NMDA to me seems to be a huge missing piece in not only ADHD but also depression and drug addiction which is a big symptom of ADHD itself. In fact, I believe that it should be strongly advised to co-administer memantine or a well devised NMDA antagonism strategy to avoid the tolerance issue which happened to me.

Another interesting effect I noticed was with anabolic-androgenic steroids. Oddly, AAS made me much more relaxed in social situations and a bit more motivated and focused. Androgens are playing a significant role in the background I’ve found. I believe not only do they impact the dopamine system behind the scenes, but also there may be cortisol and other problems. In a roundabout way, ADHD seems to cause extreme anxiety in social settings over time due to self-consciousness and poor social outcomes over time. Increased cortisol seems to decrease endogenous testosterone. Decreased endogenous testosterone causes all kinds of problems including memory problems, increases obesity, etc.

In the end, I think ADHD needs to be headed off at the pass early with stimulants. Otherwise it snowballs and wreaks all kinds of havoc.

With that all being said, I’m hoping that nootropics help my poor social abilities, problems focusing, and completion of tasks. It’s hard to say what is ADHD and what is a comorbid problem though. So far the nootropics seem to deliver.

REPORT ABUSE

[Author]

Posts