217 replies to this topic

[Animal]

I take it you never had reason to try the valproate ?

Everything that I'm taking is neurotrophic, which beyond Valproate's mood stabilizing properties, is why a number of people take similar agents---like Lithium.

Dude, Vyvanse is far from neurotrophic.

[Rational Madman]

I take it you never had reason to try the valproate ?

Everything that I'm taking is neurotrophic, which beyond Valproate's mood stabilizing properties, is why a number of people take similar agents---like Lithium.

Dude, Vyvanse is far from neurotrophic.

Well, you're right, I probably shouldn't have placed Vyvanse in that group, because its inclusion has no basis in evidence that I've encountered. Indeed, I was just making an assumption based on my knowledge of its mechanism, which by my own admission, isn't close to infallible. At the same time, though, I was under the impression that deleterious effects required either chronic monotherapeutic use, and the sustained administration of doses far above the suggested dose range. Since you've distinguished yourself as an amphetamine skeptic, do you mind sending some of the studies that shaped your views---but only if you have them in a folder in your hard drive?


On a separate note, how's graduate school going?

[Rational Madman]

Speaking of my dog, I took this startling picture today:



Yes, he's a total bad ass.

Edited by Rol82, 21 November 2010 - 03:02 AM.

[justwalkingaround]

I'd like to say that I have never read such detailed insights as I have read in this thread, lol, although I could easily be bamboozled since the level of detail exceeds anything I know.

You had mentioned Cerebral Health's 'memeron', and later its synaptic excel powder. Do you believe either of these enhance cognition, and if so, which do you feel may be superior?

I am a 40-something year-old planning on re-entering college, and I am trying to grasp the recommendations/experiences in this forum, but unfortunately I lack the necessary understanding to make an informed decision. I am an average student with average aptitude and I would like to enhance my innate ability, but I am certainly not interested in 10 supplements and/or medications--instead, I am interested in a simplified yet effective approach that may include a total of 3 supplements or medications.

I have tried memory supplements in the past, and I am disenchanted with the results.

I am not against the pharmacological approach, but I would indeed like to minimize that approach.

Perhaps it would be best to see a list of Rol82's top 3 supplements, and then a list of Rol82's top 3 medications.


I am thinking Modafinil (but i would opt for adrafanil due to simplified availability) and Synaptine Excel powder near the top?


suggestions welcome by all.

On a separate note, Rol82, have you ever considered N-back training? Do a search for 'brain workshop' in google. I use the standalone version, and I configure the config.ini file to adjust the level of interference, increasing it before going to the next level. You may need to adjust your sounds and audio device applet's advanced, performance tabs and bring down hardware acceleration and sample rates to midlevel to prevent sound drops.

They also have a forum you may find interesting, as there are a few very sharp contributors.

[Rational Madman]

And while at my brother's apartment, where he's much more studious, and considerably more agreeable:

Edited by Rol82, 22 November 2010 - 06:16 AM.

[rwac]

Speaking of my dog, I took this startling picture today:

Did you throw him a piece of meat or something, because that pic doesn't seem to make sense.

[Rational Madman]

Speaking of my dog, I took this startling picture today:

Did you throw him a piece of meat or something, because that pic doesn't seem to make sense.

Yes, the picture was staged, of course. However, he is named after a famous character from the Blaxploitation era of film, does anyone care to guess?

Edited by Rol82, 21 November 2010 - 03:35 AM.

[rwac]

Yes, the picture was staged, of course. However, he is named after a famous character from the Blaxploitation era of film, does anyone care to guess?

Shaft of course is the obvious guess. The Mack ?

[Rational Madman]

Yes, the picture was staged, of course. However, he is named after a famous character from the Blaxploitation era of film, does anyone care to guess?

Shaft of course is the obvious guess. The Mack ?

No, Hammer, played by Fred Williamson. Although we did consider naming him Roundtree.

[medievil]

Okay, it has been quite some time since I've written about my regimen, and this should be interpreted as a rather positive development. Because it represents an indication of feeling qualitatively better, and in all honesty, I am feeling subjectively better. I for instance, no longer feel compelled to spend hours obsessing about my health, there has been an improvement in all symptom categories, and as a consequence, I'm living a happier and more productive life. Will my regimen work for everyone? Probably not. Am I doing something right? It's very likely. Do I care to spend hours determining the causative weight of each component. Not particularly. What have I learned from experience? Supplements and medication certainly help a great deal, but not enough of an emphasis is being placed on addressing environmental variables. Which means that most subjects should consider behavioral therapy, diverse environments, a rich social life, and a rewarding career of purpose to be especially worthy remedies. But since this is a thread on my regimen, I suppose I'll provide a detailed update of where I'm at presently.

Diet: I'm not as fanatical as I used to be, combining pleasurable foods with exceptionally healthy foods daily. I'm not a practitioner of calorie restriction (nor do I have the slightest interest in doing so), I don't exclude items from my diet because of unfounded suspicions about ostensible intolerances, and I don't force myself to eat copious amounts of fruits and vegetables. Rather, I eat fish and lamb for protein on most days, I satisfy my caloric needs, use very liberal amounts of spices, use olive oil as a condiment in most meals, drink a lot of tea and water (but a good amount of diet soda as well), eat a lot of chocolate (at least 85% cocoa), eat a jar of artichokes or a bag of freeze dried kale daily, enjoy a bag or two of frozen cranberries, will usually have some French pastries, drink about a carton of almond milk, smoke a pipe or cigar without fail, religiously drink wine and single malt scotch in the evening, eat a small amount of grains, and usually consume two or three sweet potatoes. So that's it, there's nothing really exceptional about my diet, I won't subject myself to the madness of measuring calories, I eat when I'm hungry, and usually most of my food is prepared by restaurants.

Exercise: Not very rigorous, just a brisk walk in the park with my dog and girlfriend, or maybe some friends on most days. On the weekends, I've been playing intense games of basketball with some buddies, I may sometimes lift weights, and when I feel up to it, I play racquet sports.

Supplements: Krill oil, Green/White Tea Extract, Ortho Mind, Glycocarn, Arginine, Magnesium Orotate, Ortho Core, Curecumin, RevGenetics' Nitro-Mx, Rev Genetics' Astral Fruit-C, Methylcobalamin, Vitamin K2, and Aleve.

Medication: Luvox, Donepezil, Strattera, Vyvanse, Rasagiline (occasionally), Modafinil, and sometimes Trazodone for sleep.

So take what you will from all of this....
But my very casual approach to my regimen should be telling.

This is a great update, and shows that everyone here is capable on getting a proper regime to adress all personal issue's.

I do wonder why you dramatically cut out of a lot of supplements? IMO that was a wise idea as we have no idea how many of those behave downstream, and has we have seen in rodent storie's they have widespread effects in differend pathway causing their beneficial effects, making it pretty impossible to predict interactions with simular compounds.

[Rational Madman]

Oh, I forgot to mention my daily use of Chia seeds as well, but I suppose this wasn't a critical omission.

[EmbraceUnity]

I like the new regimen. Very much agree.

[Connor MacLeod]

I strongly disapprove. You forgot the disclaimer but I will do it for you: Kids, don't try this at home!

You're absolutely right, and from henceforth, discussion will be confined to agents that can be procured through normal channels. However, private inquiries about the additional constituents of my cocktail will be responded to in some circumstances provided that they not be posted or discussed in any imminst threads. I want to echo Kismet's comments, and urge users to not proceed carelessly with the use of prescription drugs.

Do you hope to work for the State Department in the future? If so, you may have some interesting security interviews to look forward too.

[FunkOdyssey]

Rol I'm curious about the dosages on some of these items in your regimen, would you be willing to update with that detail?

[Logan]

So do you notice a discernible difference with donepezil? Why did you start taking this? I'm assuming it was simply to elevate cognitive function in some way.

[Rational Madman]

I strongly disapprove. You forgot the disclaimer but I will do it for you: Kids, don't try this at home!

You're absolutely right, and from henceforth, discussion will be confined to agents that can be procured through normal channels. However, private inquiries about the additional constituents of my cocktail will be responded to in some circumstances provided that they not be posted or discussed in any imminst threads. I want to echo Kismet's comments, and urge users to not proceed carelessly with the use of prescription drugs.

Do you hope to work for the State Department in the future? If so, you may have some interesting security interviews to look forward too.

Well, I appreciate the sanctimonious concern, but I've already been subjected to background checks, and without incident. And I've interned at the State Department before, so I have no concerns about future employment at Foggy Bottom. But in any case, I have plenty of employment options. Furthermore, I blend in with considerable ease, which I suppose is made easier by the fact that my private life isn't confined to attending Highlander conventions.

Edited by Rol82, 21 November 2010 - 06:48 PM.

[Connor MacLeod]

I strongly disapprove. You forgot the disclaimer but I will do it for you: Kids, don't try this at home!

You're absolutely right, and from henceforth, discussion will be confined to agents that can be procured through normal channels. However, private inquiries about the additional constituents of my cocktail will be responded to in some circumstances provided that they not be posted or discussed in any imminst threads. I want to echo Kismet's comments, and urge users to not proceed carelessly with the use of prescription drugs.

Do you hope to work for the State Department in the future? If so, you may have some interesting security interviews to look forward too.

Well, I appreciate the sanctimonious concern, but I've already been subjected to background checks, and without incident. And I've interned at the State Department before, so I have no concerns about future employment at Foggy Bottom. But in any case, I have plenty of employment options. Furthermore, I blend in with considerable ease, which I suppose is made easier by the fact that my private life isn't confined to attending Highlander conventions.

I wasn't being sanctimonious, just trying to give you a heads up. I've avoided the use of any non-prescribed pharmaceuticals, scheduled or otherwise, just to avoid uncomfortable questions. Best of luck to you.

THERE CAN BE ONLY ONE!

[EmbraceUnity]

Highlander is awesome.

[DairyProducts]

Highlander is awesome.

This probably doesn't belong in a forum about trying to live longer, but I'll write it for the Highlander fans out there.
In college, I saw some people play a drinking game to the first highlander. The rules were that you had to drink a beer every time the time jumped or someone got killed. In order to win you had to not vomit or urinate for the duration of the film and the credits, at which point the winner gets to yell "There can only be one!" Most people are incapable of doing this (it's right under two hours and around 20 beers), but I knew two who did. Do with this knowledge what you will.

[aLurker]

Highlander is awesome.

This probably doesn't belong in a forum about trying to live longer, but I'll write it for the Highlander fans out there.
In college, I saw some people play a drinking game to the first highlander. The rules were that you had to drink a beer every time the time jumped or someone got killed. In order to win you had to not vomit or urinate for the duration of the film and the credits, at which point the winner gets to yell "There can only be one!" Most people are incapable of doing this (it's right under two hours and around 20 beers), but I knew two who did. Do with this knowledge what you will.

"There can be only one!" - yet two made it. I feel like we must add some kind of sudden death challenge if more than one endures the entire movie, preferably a challenge involving swords.

[BuddhaHands]

Rol!

I find your regimen amazing like many others in the thread. I'm curious if you appear and act as it seems you feel through your descriptions. This might be the creepiest request you've received, but I also live in The District and am wondering if you'd like to meet for coffee or something. Perhaps I could serve as some kind of testimony to the rest who are skeptical about the regimen?

Let me know if you're interested

[aLurker]

Rol!

I find your regimen amazing like many others in the thread. I'm curious if you appear and act as it seems you feel through your descriptions. This might be the creepiest request you've received, but I also live in The District and am wondering if you'd like to meet for coffee or something. Perhaps I could serve as some kind of testimony to the rest who are skeptical about the regimen?

Let me know if you're interested

Testimony? I don't think anyone doubts that he's alive and lucid. You'll have to come up with a better excuse than that, perhaps you have some candy in your van?

[BuddhaHands]

Testimony? I don't think anyone doubts that he's alive and lucid. You'll have to come up with a better excuse than that, perhaps you have some candy in your van?

I still have Milky Ways from Halloween? Haha, I started lurking the forums about a month or two ago and have been toying with Piracetam (+choline/inositol), DLPA, a multi-vitamin and fish oil for some time. Saw Rol's epic regimen and figured, 'why not ask?'

[Rational Madman]

Rol!

I find your regimen amazing like many others in the thread. I'm curious if you appear and act as it seems you feel through your descriptions. This might be the creepiest request you've received, but I also live in The District and am wondering if you'd like to meet for coffee or something. Perhaps I could serve as some kind of testimony to the rest who are skeptical about the regimen?

Let me know if you're interested

As I've indicated, I'm working off-site in Iowa City, supporting my girlfriend and possible future wife---I've found myself looking at engagement rings. So I'm not in the District, but I still have my apartment there, and my visit will likely be imminent. However, I'm a bit hesitant, since there isn't much substance to our relationship, which might make our first encounter exceedingly awkward. And because I don't want to feel like a jerk if I find myself suspiciously receiving an urgent call in the midst of our meeting, and making a desperate escape through the emergency exit. If we do meet, lower your expectations, and don't expect that we'll be best friends forever. But to your advantage, you do seem normal, though, and I don't see why I wouldn't be able to spare at least 15 minutes with a well meaning stranger in a public setting.

[brunotto]

Sure Pioglitazone is less dangerous than Acitretine...
http://www.ncbi.nlm....pubmed/16038845
http://www.ncbi.nlm..../pubmed/2970477

Edited by brunotto, 01 January 2011 - 10:27 PM.

[Rational Madman]

Sure Pioglitazone is less dangerous than Acitretine...
http://www.ncbi.nlm....pubmed/16038845
http://www.ncbi.nlm..../pubmed/2970477

Well, both drugs have their dangers, and at this time, it's difficult to say which agent is more ideal for targeting liver x receptors, which was the reason behind my use of Acitretin. But while taking Acitretin, I didn't experience anything profound, which I suspect might be due to bioavailability issues, or the neutralizing side effects. However, I do think that the guidelines and warnings of the perils of Vitamin A use are a bit hysterical, and perhaps detrimental to some, because it assumes that Vitamin A needs are static regardless of pathology. Pioglitazone and Rosiglitazone are also interesting candidates for this target, but the incidence of cardiac events prevents wider use, and may lead to the suspension of the latter.

Although I promised myself not become too invested into the calibrating of my regimen, I decided that since we are at the dawn of a new year, it might be worth one last assault, because I think for the time being, I've come as far as I possibly can. Here is my regimen at present:

Geronova's Dihydrolipoic Acid- 2 capsules. Although Michael Rae will certainly object to my choice of dihydrolipoic acid, I've decided that using the metabolite makes more sense, because I imagine its effects should be less indeterminate than R-Lipoic Acid. I know, I'm departing from empiricism, but sometimes the standards for proof can be a significant obstacle to scientific discovery.

AOR's Advanced Bone Protection and Strontium-1 capsule. I'll give this a fair trial, because I want something more powerful than just Strontium and Vitamin D3, and don't want to take large doses of K2 or calcium.

Bluebonnet's Ubiquinol-1 to 2 capsules. On one hand, it may not be necessary to use, but I'm dubious about its ostensibly deleterious effects, and because of the striking presence of mitochondrial dysfunction in studies of disease pathology, I think it's worth supplementing.

Life Extension's Peak ATP: 4 tablets. I've concluded that cognitive outcomes are dependent in no small part on optimal levels of nitric oxide, and thus, ample cerebral blood flow. When I become older, I might worry more about coagulation factors, but not for now. But Glycine Propionyl Carnitine has multiple properties that many might find appealing, and after research, it seems like it's several steps above the more popular Acetyl Carnitine.

AOR's Advanced B Complex-3 capsules. I'm back in the B-vitamin camp, and decided to include this supplement in order to maintain optimal levels of methylation.

Bluebonnet's Super Antioxidant Formula-3 capsules. This is an excellent formulation, and indicative of Bluebonnet's pleasing trajectory towards creating more empirically sound formulas.

Revgenetics' Master Gene P-16-2 capsules. This agent is understudied, but I'm interested in it's potential for curbing inflammation, maintaining cellular integrity, and catalyzing repair mechanisms to address mutations that may lead to a cascade of beguiling effects.

Revgenetics' Master Rx-2 capsules. I have my reservations about Resveratrol, but I also think that many of the negative findings have been due to poor study design---which is the case for most negative findings in supplement studies. What gives me confidence is my understanding of its pharmacology, and its potential if half-life and bioavailability problems are overcome. Revgenetics' Nitro-Mx is moving in the right direction, but I've gone a step further, and have changed my strategy for administration. At night, and so I won't diminish the effects of Astral Fruit C, I take the following: two tablespoons of olive oil, a teaspoon of black pepper, a variable amount of lime juice, a half a bottle of wine, a variable amount of Chia Seeds, Ubiquinol, Master Gene P16, a teaspoon of lecithin, fat soluble nutrients, dihydrolipoic acid, and a multi-antioxidant formula. For the time being, this seems to work well, but I will probably make future modifications.

Life Extension's Essential Fat Soluble Nutrients-1 capsule, and my replacement for all of the other fat soluble supplements that I formerly took. This is a well formulated supplement, which is keeping with Life Extension's commitment to thoughtful engineering. However, I only wish that Life Extension was more committed to higher standard of quality control, which comes at the expense of delivering more affordable products. Because some consumers are more concerned with the methodology of sourcing and manufacturing, I think it would behoove them to introduce two separate product lines, for the pedestrian, and for the neurotically health conscious.

AOR's Methylcobalamin Ultra-1 lozenge. I've become a bit wary about creating an imbalance with other B-Vitamins, or aberrant methylation, but I think the benefits of taking 15 mg exceeds the costs.

Cerebral Health's Synaptine Ultra-1-2 capsules, but I'm becoming increasingly dubious about ostensible nootropics. Anyway, I needed something with a strong affinity for AMPA receptors.

RevGenetics' Astral Fruit C-3 capsules, I'm somewhat optimistic about its potential, but I'm looking for a drug alternative. It also occurred to me that this supplement is needed for immuno-competency, since many of the more popular supplements have immunosuppressive qualities.

E-Lyte's Sodium Butyrate-In transit, and used for histone deacetylase inhibition, and reelin promotion. Further, it possesses the desired pharmacological properties of Valproate, but in contrast, seems to be a bit more sparing on one's cognition.

E-Pharm's Testforce (contains Sarcosine, pretty cool)-2 scoops, and used as a testosterone booster, neuroplaticity aid, and broad spectrum cognitive enhancer. My use of this supplement should be evidence of my disdain for the excitotoxic hysteria.

AOR's Prostaphil-3 capsules, and used to mitigate the adverse effects of Testforce, and to amplify detoxification mechanisms.



Vyvanse-30 mg
Strattera-40 mg
Modafinil-200 mg
Luvox-50 mg
Mirtazapine-15 mg
Donepezil-10 mg
Rasagiline-1-2 mg
Metformin-250mg

For supplements, I'm toying with the notion of adding one of the following, but will probably not make any amendments:
Magnesium Orotate

Nattokinase

Bacopa

Iodoral

Pycnogenol

Vimmortal

Neygeront ampoules

Acetyl Cysteine

Glucosamine




As for drugs, I'm contemplating taking Minocycline, Diflucan, Cycloserine, and Valtrex on a weekly basis. And I might include a small amount of dessicated thyroid hormone, but I'm quite hesitant. I'm also giving Piogltiazone, Buspirone, Clonidine, and Ondansetron second looks, but I'll certainly not be using all of these drug candidates, and will probably leave my drug regimen in its current shape. Indeed, I'm a bit wary of trying to take control of all variables, because it's not a healthy endeavor. Anyway, the pharmacological targets that have left me in a bit of a limbo are the liver x receptors, and the phosphodiesterase enzymes, because there aren't many good agents available.

With that said, I apologize for my erratic mood as of late, and for my failure to respond to all inquiries. My mercurial mood has been owing to some acrimony with a long standing friend, and the mild-depression and increased alcohol consumption that followed our mutual decision to de-link. But, our significant others conspired to reconcile the both of us, and all is better---we couldn't bear the notion of not being connected. As for inquiries about lifestyle, drugs, supplements, and multiple physiological disturbances, I've been purposely distant. This is not because I have developed a sudden callous attitude towards the suffering of others, but because I concluded that I don't have all of the answers, and have the humility to not render advice about fields which I lamentably have only a limited formal education. At this point, it should be abundantly clear that a number of individuals in this community have chronic and pervasive disorders that manifest in multiple forms. And evidently, many have grown alienated with the inability of medical professionals to adequately treat these confounding disorders, and as a consequence of this disenchantment, they have adopted a self-help posture. This is a generally positive development, because it's an acknowledgment that professional pressures and obstacles prevent optimal patient outcomes in these disorders. But at the same time, there are so many different etiologies (proven or postulated) for many of the oft reported symptoms of fatigue, cognitive dysfunction, and mood disturbances, and consequentially, I don't feel entirely comfortable with making prescriptions. Because I could be terribly wrong, and in this failure, I may contribute to hindering personal recovery. An individual sense of wellness is the most acute, and because of this acuity, the individual is in the best position to care for personal health needs if they can summon the energy to apply themselves. In contrast, medical professionals and discussion participants like myself are at a great disadvantage, because we're not fully cognizant of patient histories, and do not possess the time to personally commit ourselves to investigation. Diagnostic manuals and the like serve as good general guides, but I think there's a frequent failure to capture the variance in symptom presentation for each disorder. Which places a substantial burden on the individual, because of their vested interest to make the appropriate treatment modifications that suit the distinctive nature of their symptoms. Although this might be an arduous process, it is in my opinion, requisite for exceptional success.

Edited by Rol82, 05 January 2011 - 03:15 AM.

[brunotto]

Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.

http://www.ncbi.nlm....pubmed/19590508
http://www.imminst.o...xtend-lifespan/

Telmisartan augmented eNOS expression, phosphorylation and NO production, which were reversed by the co-treatment of GW9662. Conclusions The present results suggest that telmisartan-induced inhibition on vasoconstriction in resistance arteries is mediated through PPARγ-dependent increase in eNOS expression and activity, which is unrelated to AT(1)R blockade


http://www.ncbi.nlm....pubmed/21156825

Edited by brunotto, 09 January 2011 - 11:10 PM.

[Rational Madman]

On the question of adding to my supplement regimen, I decided on Bluebonnet's Super Quercetin, which should be highly synergistic with other components of my regimen. And since I have a few underutilized bottles, I may add Vimmortal for a period.

Edited by Rol82, 24 January 2011 - 12:05 AM.

[Rational Madman]

Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.

http://www.ncbi.nlm....pubmed/19590508
http://www.imminst.o...xtend-lifespan/

Telmisartan augmented eNOS expression, phosphorylation and NO production, which were reversed by the co-treatment of GW9662. Conclusions The present results suggest that telmisartan-induced inhibition on vasoconstriction in resistance arteries is mediated through PPARγ-dependent increase in eNOS expression and activity, which is unrelated to AT(1)R blockade


http://www.ncbi.nlm....pubmed/21156825

I considered this class for its targeting of the aforementioned group of nuclear receptors, and adding to my interest, I've found the price for generic Telmisartan to be quite reasonable. However, I suppose I'm still wondering about the ideal dose/kg in normal human subjects. Anyway, the following should also be of some interest:

Curr Pharm Des. 2004;10(25):3177-84.


New classes of AChE inhibitors with additional pharmacological effects of interest for the treatment of Alzheimer's disease.
Villarroya M, García AG, Marco JL.

Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, 28029-Madrid, Spain. mercedes.villarroya@uam.es


Abstract
Alzheimer's disease (AD) is associated to a gradual loss of attention and memory that have been associated to impairment of brain cholinergic neurotransmission, particularly a deficit of cholinergic neurons in the nucleus basalis of Meynert. Thus, it is not surprising that the first therapeutic target that has demonstrated therapeutic efficacy on cognition, behaviour and functional daily activities has been the inhibitors of acetylcholinesterase (AChE), i.e. tacrine, donepezil, rivastigmine and galanthamine. But not all inhibitors of AChE have the same potency to block the enzyme and have a different pharmacological profile. For instance, rivastigmine is a dual inhibitor of AChE and butyrylcholinesterase (BuChE), and galanthamine is a mild inhibitor of AChE and an allosteric potentiating ligand of neuronal nicotinic receptors for acetylcholine (nAChRs). In addition, we have recently found that galanthamine has neuroprotective effects by inducing calcium signals and the induction of the antiapoptotic protein Bcl-2. In this frame, we have been synthesizing new tacrine derivatives that keep their ability to inhibit AChE but that interfere with neuronal calcium overloading and prevent apoptosis. Some of these compounds exhibit neuroprotecting properties and thus, could be useful in the treatment of neurodegenerative and ischaemic brain diseases.

Edited by Rol82, 24 January 2011 - 12:07 AM.

[Rational Madman]

Thus, telmisartan inhibits the cytokine-induced expression of the VCAM-1 gene by blocking NF-kappaB activation independently of PPAR gamma activation. Although the mechanism by which this occurs remains unclear, our findings suggest that telmisartan-induced anti-inflammatory effects might have favorable effects on vasculature in hypertensive patients.

http://www.ncbi.nlm....pubmed/19590508
http://www.imminst.o...xtend-lifespan/

Telmisartan augmented eNOS expression, phosphorylation and NO production, which were reversed by the co-treatment of GW9662. Conclusions The present results suggest that telmisartan-induced inhibition on vasoconstriction in resistance arteries is mediated through PPARγ-dependent increase in eNOS expression and activity, which is unrelated to AT(1)R blockade


http://www.ncbi.nlm....pubmed/21156825

I considered this class for its targeting of the aforementioned group of nuclear receptors, and adding to my interest, I've found the price for generic Telmisartan to be quite reasonable. However, I suppose I'm still wondering about the ideal dose/kg in normal human subjects. Anyway, the following should also be of some interest:

Curr Pharm Des. 2004;10(25):3177-84.


New classes of AChE inhibitors with additional pharmacological effects of interest for the treatment of Alzheimer's disease.
Villarroya M, García AG, Marco JL.

Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, 28029-Madrid, Spain. mercedes.villarroya@uam.es


Abstract
Alzheimer's disease (AD) is associated to a gradual loss of attention and memory that have been associated to impairment of brain cholinergic neurotransmission, particularly a deficit of cholinergic neurons in the nucleus basalis of Meynert. Thus, it is not surprising that the first therapeutic target that has demonstrated therapeutic efficacy on cognition, behaviour and functional daily activities has been the inhibitors of acetylcholinesterase (AChE), i.e. tacrine, donepezil, rivastigmine and galanthamine. But not all inhibitors of AChE have the same potency to block the enzyme and have a different pharmacological profile. For instance, rivastigmine is a dual inhibitor of AChE and butyrylcholinesterase (BuChE), and galanthamine is a mild inhibitor of AChE and an allosteric potentiating ligand of neuronal nicotinic receptors for acetylcholine (nAChRs). In addition, we have recently found that galanthamine has neuroprotective effects by inducing calcium signals and the induction of the antiapoptotic protein Bcl-2. In this frame, we have been synthesizing new tacrine derivatives that keep their ability to inhibit AChE but that interfere with neuronal calcium overloading and prevent apoptosis. Some of these compounds exhibit neuroprotecting properties and thus, could be useful in the treatment of neurodegenerative and ischaemic brain diseases.

Oops, in my previous entry, I pasted the wrong abstract. I guess I had too many tabs open at the time. Anyway, here's what I intended to paste:

Effects of ACE-inhibitors on learning
and memory processes in rats
by
Nikolova JG, Getova DP, Nikolov FP.
Department of Physiology,
Higher Medical Institute,
Plovdiv, Bulgaria.
Folia Med (Plovdiv) 2000;42(1):47-51

ABSTRACT

INTRODUCTION: Besides their well known effect on systemic blood vessels and heart, ACE inhibitors are supposed to have an effect on CNS by changing the local peptide-protein system. AIM: To study the effect of ACE-inhibitors on learning and memory processes using active and passive avoidance. MATERIAL AND METHODS: Male Wistar rats were used; the animals were divided into 4 groups of 20 animals each. Distilled water (group C), captopril 1.5 mg/kg (group E1), trandolapril 2 mg/daily (group E2), and oxiracetam 0.1 mg/kg (group E3), respectively, were given orally 60 minutes before the test. Active (shuttle box) and passive (step-through) avoidance tests with standard configuration were used. RESULTS: The experimental and control animals increased the number of avoidances during the learning session of the active avoidance test; groups C, E1 and E2 showed no change in the number of escapes and intertrial crossings; in group E3 animals both variables were decreased. In memory retention test the experimental animals increased the number of avoidances in comparison to the controls. No difference was found in the number of escapes and intertrial crossings. In passive avoidance test all animals showed prolonged latencies during the learning session. In the early and late retention test prolonged latencies were found only in the experimental animals. CONCLUSION: The ACE inhibitors captopril and trandolapril improve learning and memory in active and passive avoidance tests comparable to the effect of the nootropic drug oxiracetam.