The mechanism of Dimebon remains unclear, but it's believed to modulate NMDA and AMPA receptors, increase catechloamine volume in the prefrontal and dorsolateral cortexes, inhibit the build up of beta amyloid proteins, and possibly inhibit acetylcholinesterase. In addition, it has a mysterious cellular cleansing mechanism, and appears to increase mitochondrial energy through a yet to be completely understood mechanism. I believe it might also reduce inflammation through its affinity for histamine receptors,but this hasn't been documented to my knowledge. Due to its multiple mechanisms--which seems to address the most important independent variables for the progression of neurodegeneration---and because of its excellent safety profile, I became quite intrigued with its potential. But given its suspicious failure in the latest clinical trial, which seems to be at odds with user experiences and other empirical evidence, I've become somewhat cautious. Because of the positive results in a well controlled Huntington's Disease study, Dimebon does appear to attenuate neurodegeneration, but I think the dosages used in recent studies are probably too low. And until more evidence emerges on the correct dosage for healthy individuals, I think I'll wait, and try other drugs in the meantime, because if I were to administer the prescribed dosage used for recent studies, a month's supply would cost approximately $1500. However, I've found an alternative supplier that's based in Ukraine, but I get the feeling that he's comfortable with supplying institutional clients in bulk----rather than individuals.However, there is one Russian drug in development that might be worthy of our enthusiasm---even though it has failed in recent Alzheimer's clinical trials. That drug is Latrepiridine, or more popularly known by the trade name of Dimebon. This drug has attracted my interest because I---like many of us---endeavor to optimize my cognitive abilities through diet, lifestyle, and supplementation. And am willing to sometimes undertake risks---that deter the average person---in pursuit of that goal. Although I have no cognitive complaints that would trouble the average person, this drug has a certain captivating allure; and because I've found a reputable source, I'm interested in incurring the financial and potential health costs of experimentation next month. The source is Life Extension Drugs, which is a company that I used for procuring some Ondansetron, which is another drug with considerable potential for cognitive enhancement, but has greater personal appeal as an antiemetic. Based on previous positions I've taken on this forum, I realize that my actions might render me a hypocrite, but I care little, since my thinking on the importation of drugs has evolved somewhat. Indeed, my previous strident stance has been replaced by a more ardent desire to maximize my earning potential, and out-perform my colleagues by as much as possible---even though there is no real animus between any of us. Anybody familiar with organizational behavior and politics, and the power of the human ego, though, may share my sentiments. The price, unfortunately, may be too prohibitive for most to contemplate---and I would take no solace from anybody else incurring the same costs---but since this drug possesses the real potential to provide significant benefits to many that have been on fruitless searches for a panacea drug or supplement, I thought I might as well mention it in a thread devoted to another noteworthy drug of Russian origin.
Thanks for an eloquent and interesting post in which you mention two substances I've never heard of before. What makes you think Latrepirdine is so promising when it comes to improving cognitive processes in healthy people? I couldn't find much about it and I'm quite unfamiliar with its mechanisms.
The same goes for Ondansetron, what was your experience with that?
As far as Ondansetron goes, the most attractive property is its anti-emetic mechanism---which is my primary motivation for procuring the drug, since I suffer from subclinical, but recurrent bouts with nausea. Through its modulation of the 5-ht3 receptors, though---which is critical for learning and memory formation---it seems to have some value for cognitive enhancement and anxiolysis. But, I think it must have some affinity for other receptors as well, because it appears to be more effective than other 5-ht3 antagonists in these regards.
Since I'm probably not going purchase Dimebon in the near future, there are other candidates that I'm considering, which include Amineptine, Cerebrolysin, Donepezil, Tolcapone, and Rasagiline. For Rasagiline, I've found a great source---with an incredible price---that offers a month's supply in the 0.5 mg dose, which would be ideal for life extension purposes, and for coadministration with the other drugs that I'm using if taken at .125 mg/day. As a tricyclic with dopamine reuptake inhibitor properties, the use of Amineptine would require that I make adjustments in my drug regimen---which I'm loath to do because of its efficacy---and the lone supplier that I've discovered is demanding a price that far exceeds the drug's relative worth. However, the drug is highly praised by David Pearce---whom I highly regard. Tolcapone also seems promising, but potentially very dangerous, and would certainly require significant adjustments be made to my current regimen. Donepezil has some appeal because its half life is considerably greater than the supplement grade of Galantamine that I currently use, but its effects on healthy adults doesn't seem to be profound, and in the absence of enzymatic dysfunction, may be a bit too risky. This leaves Cerebrolysin, which may be the most tolerable and safest addition, and could potentially yield the best results if used at an effective dose of 10ml per day. This source seems to be the best at the moment http://www.rxpharmac...rebrolysin.html, unless anyone can offer any alternatives that I've overlooked.
Anyway, although this thread might be the inappropriate place to post my regimen, some people have made inquiries in the past, and since this thread is devoted to the use of a drug with mood and cognitive enhancing properties---and as I imagine the previous content of my post has aroused some curiousity---I think I might as well provide a list of drugs and supplements that I've found to be immensely helpful in pulling myself out of my post-graduate state of dysthymia---which interested users may consider as an alternative to ordering Cerebrolysin. While expensive, my regimen is designed to aggressively address all of the important variables of ageing: enzymatic dysfunction, inflammation, enhanced monoamine reuptake, neuronal death, mitochondrial dysfunction, altered gene expression, etc.
Drugs
Vyvanse--30 mg---Debatably safe, tolerable, effective, and for me, inseparable.
Strattera--80 mg---At higher doses, it increases the cortical volume of acetylcholine, reduces the volume of glutamate, and increases frontocortical catechloamine volume.
Mirtazapine--30 mg--One of the few antidepressants that has been noted for its distinctive memory enhancing properties, which becomes more appreciable at higher doses.
Luvox 150 mg--An underrated antidepressant that is free of stupefying effects when administered at low doses, and is especially effective for controlling obsessive-compulsive behavior. I was previously a long term user of Zoloft, but I prefer the serenity that Luvox provides---which is considerably less activating.
Minocycline--100 mg---Used for neuroprotective purposes---it mechanistically inhibits 5-lox, and appears to reduce the volume of glutamate---in addition to other virtues. Due to potential complications, though, it's best administered at low doses.
Cycloserine--250 mg---Used for its anxiolytic properties, but the drug has multiple applications, and has gained considerable appeal as a novel cognitive enhancer.
Hydergine---20 mg---Since I've become somewhat dubious about the strength of its causal relationship with the onset of fibrosis, and because a long-term, high dose study conducted by Cucinotta, et al. seems to lend credence to past claims about its safety and enhanced efficaciousness at higher doses, I consequentially started a high dose trial. Although it would be premature to report its effects, I believe the drug has some potential as a mood stabilizer, or an anxiolytic when administered at higher doses. Presently, I'm taking 20 mg a day in two divided doses, but I may titrate to 40 mg/day---in accordance with the long term study that I cited.
Nystatin--500,000 units---Used to reduce the likely fungal proliferation that occurs with long term antibiotic use.
Ondansetron: Still in transit.
Drugs that I've used in the past, which might have some appeal to users:
Low Dose Amisulpride: This drug loses its effectiveness relatively quickly---probably due to a change in affinity.
Low Dose Naltrexone: At the risk of incurring the wrath of its indefatigable advocates, I believe that its utility is greatly exaggerated, and seems effective only as a mood enhancer and possible analgesic. I found its effects to be somewhat noticeable, but not enough to justify continued use, and until more evidence emerges, I have no intention of resuming use. Minocycline is a much more palatable alternative, and is supported by far more convincing empirical evidence. However, there is some evidence that naltrexone may have cognitive enhancing properties at higher doses.
Buspirone: I tried this for a week, but in all honesty, I didn't have the patience to wait for its effects to become appreciable---which in any case, seems to be rather mild. For better results, users should stick with SSRIs, which have the advantage of not having an antagonistic affinity for D2 receptors---a mechanism that may lead to problems for some users at higher doses.
Supplements
1. Cerebral Health's Memeron: 2 capsules per day: Probably the best memory enhancer in the supplemental marketplace, and far superior to the garbage product that Life Enhancement produces.
2. AOR's Orthocore: 6 capsules per day: Deserving of its reputation as the best multivitamin on the market, and when taken religiously, a subjective improvement can definitely be felt. Although I would prefer a greater quantity of flavonoids in the formula, I think this product exceeds most in addressing the health needs of the average individual, and should therefore be an indispensable component of any regimen.
3. Cerebral Health's Synaptine Excel: 2 capsules per day, but not every day: Although it's debatable, I think Oxiracetam is probably the best overall -racetam in terms of half-life, potency, subjective enhancement, and effectiveness with healthy individuals.
4. Life Extension's Mitochondrial Energy Optimizer: 4 capsules per day: Covers most of the basics of enhancing mitochondrial function, but is not without its deficits: Coenzyme Q-10, and because of its inclusion of luteolin and carnosine, it's marginally better than AOR's Mito-Charger.
5. Nordic Natural's Ultimate Omega: 6 capsules per day: I haven't decided on the relative superiority of EPA or DHA, since there is evidence supporting both of their supplemental use. If forced to choose, I would opt for EPA, but until the controversy becomes satisfactorily decided, I'll stick with a balanced formula that favors EPA. Once it's picked up by vendors, I think AOR's Omega 3 Vegan is worth a trial, though.
6. AOR's Methylcobalamin Ultra: 2 lozenges per day: An underappreciated neuroprotector that can be safely administered in doses larger than what is suggested in the dosage guideline---even the 30 mg that I take daily.
7. Revgenetic's NitroMx: 2 capsules daily: Sure, resveratrol has been oversold, but it still remains an effective broad spectrum supplement that is worth including in any regimen.
8. AOR's Curecumin: 2 capsules daily: Another panacea supplement, and it appears that AOR has solved the bioavailability problem that renders many Curcumin supplements next to useless.
9. AOR's EGCG Max: 3 capsules daily: The evidence supporting the use of green tea is quite compelling, and since I dislike caffeine, I decided to include this supplement.
10. Revgenetic's Master Cleanse P-16: 1 capsule daily for a week, and resumed a week later: I'm a bit intrigued by the mechanism of this supplement, which may be a powerful enhancer of cellular health---among other interesting attributes.
11. AOR's Benagene: 1 capsule daily: Although I was initially skeptical, there is increasing evidence that validates some of the mechanistic claims of the inventor and manufacturers, which I believe warrants the price.
12. Bluebonnet's Super Quercetin: 8 capsules daily: Used primarily for its utility in the degradation of histamine, but the constituents of this formula possess multiple properties that don't require reiteration.
13. Nicoderm Patch: Although many use the patch for enhancing focus, I find the use of a single patch to be highly motivating, and quite useful as a learning aid and for supplementing my neuroprotectective firewall.
14. Life Extension's Timed Release Melatonin: 1 capsule: An effective sleep aid when administered at 3 mg, which I believe to be the most effective dose.
15. AOR's Ortho Mind: 3-6 capsules when needed: This formula includes ingredients that broadly covers the needs for optimal neurological health, and is far superior to the formulas of competitors that either choose the wrong ingredients or fail to provide sufficient quantities in each serving.
16. Healthy Origin's Ubiquinol: 1 capsule daily: In healthy individuals, the use of Coenyme Q10 is highly debatable, but using its reduced form should be less problematic, and the degree of the markdown on this product made it irresistible.
17. Revgenetic's Astral Fruit C: 2 capsules daily for a one week on and one week off cycle: Even if you're not completely convinced by the rationale for the product, Revgenetics offers a highly concentrated form of astragalus, which has a great deal of use for producing a healthy immune response.
18. My morning concoction, which contains kefir, thawed goji berries, goat's milk whey, brown rice protein powder, cinnamon, ginger, and cocoa powder. Of course, this shouldn't be classified as a supplement, but I thought it was worthy of inclusion.
Diet, Exercise, and Lifestyle
Although many enjoy the narcotic quality of exercise, I think an alternating brisk walk/ light jog in the park for an hour each day is more than sufficient---unless, of course, you need to reduce your weight, improve insulin sensitivity, etc.. This is supplemented by a few days of light anaerobic exercise, with an added emphasis on light. As for my diet, there is some caloric restriction---but not to an extreme degree. More importantly, its rich in flavonoid dense foods, seafood, nuts, spices, and seeds, but in addition, small quantities of meat and grains are consumed. Although I have my occasional reclusive periods, I force myself to remain socially active, and exposed to diverse environments of stimuli. This can be highly elevating, even if it's sometimes accompanied by moments of agony---boring dates, facile people, etc. Although I have no philosophical objection, I've never used illicit narcotics, but my alcohol consumption probably fits the operational definition of moderate----mostly including wine and cognac. To shield my body from stress, I rely heavily on Mozart, meditative exercises, and the occasional therapeutic massage. Even though my current stress level is not problematic, I'm also considering investing in a cranial electric therapy device, but I've found the supporting evidence to be underwhelming.
Anyway, I apologize for my narcissistic deviation from the topic, but once I started typing, I decided to finish what I originally intended to compose.
Edited by Rol82, 10 August 2010 - 03:33 PM.