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Stimulation of nicotinic repectors via non-nicotine substances....

Teratogenicity isn't really a concern if you're not planning on having kids anytime soon...

Anywho, nicotine itself isn't too bad; it's the carcinogens associated with tobacco (N-nitrosonornicotine, nicotine-derived nitrosamine ketone, benzo(a)pyrene) combined with the fact that nicotine becomes significantly more addictive when administered with a monoamine oxidase inhibitor:

http://dx.doi.org/10.1523/JNEUROSCI.2139-05.2005

http://dx.doi.org/10.1016/S0091-3057(03)00223-5

this latter fact meaning that delivery of pure nicotine via patch, gum, inhaler, etc. is less problematic than the usage of any tobacco product (natural clearly does not mean safe in this case!).

Smoking anything is just a bad idea in general, cannabis may escape carcinogenicity (or so we think; the jury is still out) thanks to CBD but pretty much any other plant you burn and inhale will probably make you regret it!

Anywho, trying to find a nAChR agonist with no addictive potential seems to me to be as silly a quest as trying to find a mu-opioid agonist with no addictive potential. Perhaps an alpha-7 selective agonist could work, but there are none of these available to the commoner and none have even been tested for safety so it certainly isn't a good idea to take them!
 
oh yeah I realised that but just relooking at the taretogenicity picture shocked me enough to warn that it maybe a bad, free alternative.
and Im not gonna have kids anytime soon, im man, and gay ontop of that.
 
Interesting topic guys!

I'm under 20mg/day (but increase to 40mg today) memantine and will try nicotine patch for there nootropic effect (for studying) the week coming! Will post my results here. Memantine might reverse or delete the onset of tolerance (I hope so hehe)

[EDIT] Didn't have enough money to buy a nicotinic patch yet but think will try soon.
 
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I just found out in another thread that Ibogaine/nor-ibogaine has some action on the nicotine receptors. Microdose?
 
yeah the problem isnt the nicotine. its the fact that you are breathing in smoke which contain carcinogens (cancer causing agents). thats why those E cigs have you breath in vapor, not smoke.
 
Limpet_Chicken said:
Bear in mind that memantine is an alpha7 nicotinic receptor antagonist.
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Can you develop a little more? Do you think memantine can't really reverse nicotine tolerance? Or not totally? I apology for posting in advanced drug discution without a strong background in psychopharmacology...
 
Alpha7 NAChR agonists are nootropic, the cholinesterase inhibitor galantamine, used for treating alzheimers, dementia etc (well not treating, merely permitting those poor accursed souls afflicted with these awful conditions to exist as something more than an ambulent, breathing cadaver for a scant handful more weeks or months) and for those seeking cognitive enhancement who are otherwise healthy, or with a non-dementia-like memory/cognitive impairment such as myself, is in addition to its AChE inhibitor properties, an alpha7 selective nicotinic receptor agonist, and seems much more effective than other cholinesterase inhibitors, I believe, due to this additional property.

I have tried both galantamine and huperzine-A (although the latter is an NMDA antagonist, although subunit-selective, I believe for NR2b-containing NMDARs, and not targeting the PCP recognition site that PCP and ket, etc go for, and likewise not targeting either the glycine or polyamine binding sites, nor acting as a pore-blocker, nevertheless this needs taking into account, I am sure, when figuring out the effects this may have on either cognitition/memory and/or opioid/stimulant etc. tolerance) and galantamine was much, much more effective for cognitive and memory enhancement.

Alpha7 nicotinic antagonists, following that line of reasoning, acting inversely, should, correspondindly, I would think, possess memory-impairing properties. I don't think this will have any effect on tolerance, but certainly I think, is likely to make it harder to remember things and think straight, causing 'brain fog' so to speak.

People who are, at baseline, not impaired in that area may not find it significant. But then again, they may. I tend to be impacted by such things, possessing cognitive/mnemonic impairing properties more than most people, as I have some rather troublesome cognitive and memory deficit issues, I believe stemming from excitotoxic damage thanks to some pretty poor decisions in my life I made several years ago, one really hideous incident involving forced, cold-turkey withdrawal from barbiturates, which I had been using to a vast excess, and several again very unpleasant withdrawals from GBL (GHB has a biphasic mode of action, being at high concentrations a GABAb receptor agonist, but it activates the GHB receptor at much lower concentrations than it does for GABAbRs, GHBr activation induces glutamate release, and selective agonists seem to be quite excitotoxic)

After all that, I am left with some memory deficit and cognitive impairment, which, while I have good and bad days, sometimes is pretty damn bad. So I tend to take into account, properties like this and their potential effects more than most people would do, or would have to.


Haven't really time to look into it right now, regarding the specific mode of action of memantine vs PCP-site noncompetitive NMDA antagonists (I.E PCP, ketamine, methoxetamine, DXM, the NMDAr antagonists most commonly used as recreational/tolerance reducing drugs) etc stuff to do, and lots of it.

Memantine is a rather odd NMDAr antagonist, with a funny mode of action at the receptor, again, I need to look into that before further posting on the subject to refresh my knowledge of it.

And thikal, I really don't think you should apologise or feel unwelcome in ADD for not being a psychopharmacology expert, I am, whilst quite the hobbyist, and autodidact in the subject, not what I could call an expert, reasonably knowledgeable and well-read, but not an employed professional, and still post here.

There are, I believe, far more commonly stupid answers, than stupid questions. Much of the time, even a poorly worded or understood question, in fact shows intelligence, the stupid wouldn't bother asking in the first place. Feel free to post here, it is how we all learn. I myself have learned quite a bit here, in ADD (amongst quite a few other places both in the subject of psychopharmacology, biochemistry and straightforward org. chem)
 
Plenty of attempts to make epibatidine analogs over the years has been set into motion.

I even had some invention ideas for projects in this field, but there would be no way of knowing until the hypothesis had been tested whether or not the idea was valid.

Interestingly, I never found nicotine gum or patches addictive although it did curb the desire to want to smoke. I am not sure how successful this chemistry would be. I would say it is the type of thing that comes along only after all the cocaine and opiate analog ideas have already been exhausted.
 
Such an interesting post Limpet!

Alpha7 nicotinic antagonists, following that line of reasoning, acting inversely, should, correspondindly, I would think, possess memory-impairing properties. I don't think this will have any effect on tolerance, but certainly I think, is likely to make it harder to remember things and think straight, causing 'brain fog' so to speak.
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Yes I definitely felt that brain fog when I increased the dosage up of memantine. But after a few days of dosing, the brain fog went away. So I feel/hope (just a feeling can be totally wrong I' aware!) that the drawback you speak about memantine are transitional.

I felt that heavy use of GBL shot my memory in a really bad way too, then I stopped. Smoke pot was a bad factor too.

I saw somewhere in the net that nicotine is a great compound with a bad delivery road (smoking). Maybe nicotinic patch or gums or sprays are great for nootropic use. But I don't want to be addicted to nicotine because at this stade you lose all nootropic effect for a shitty mood. I think nicotine analogues are promising for a great nootropic effet, that's why I listen to your post attentively! :) Chain-smoke cigs is not good for a nootropic effect.


Interestingly, I never found nicotine gum or patches addictive although it did curb the desire to want to smoke. I am not sure how successful this chemistry would be.
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Really interesting! I have to try it. Did you find any significant nootropic effect for nicotine patch alone?

EDIT: Oh and I apology I read the title's topic again and it's not about nicotine, my posts were a little off topic...
 
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I took nicotine substitution therapy to help with a smoking addiction, not for nootropic effect.

I can only suggest that the reason drugs like ABT-594 are not available to the public is that there must be something wrong with this sort of chemistry.
 
Jamshyd said:
If I'm not mistaken, Galantamine, a substance generally sold as a nootropic, has some action on nicotinic receptors.

Some of the drugs prescribed for demential/parkinsons/alzhiemers are nicotinic agonists.

Keep in mind that all of the above are prone to producing nausea in some people...

L-Huperzine A is an Acetylchollinesterase inhibitor (non-toxic at reasonable doses - and in fact classed as nootropic), so that might help. From my experience, it is one of the most useful OTC substances for both mood and cognitive enhancement, and a friend has found it helpful when she quit smoking.

As an aside, later I found out that L-Huperzine A also has some NMDA-antagonist properties, heh.
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Crimethink said:
Whitespy- have you tried Chantix (Varenicline) the nicotine partial agonist? Possibly with Galantamine to increase its efficacy?

If you use the patches or the inhalers you can consider mecamylamine to make them more effective & prevent tolerance buildup. (Mecamylamine increases binding of nicotine with or without tolerance) The stuff is readily available & fairly inexpensive, too.

Nicotine patches are safe except for the cardiovascular effects which aren't a problem in a healthy person when you aren't dumping in radicals & toxins from smoke. If you think its a problem consider the Mecamylamine so you can use less. With the exception of two negative effects I detail below nicotine is pretty safe relative to smoke or snuff.

Nicotine seems to have some long term advantages too. You probably know it reduces the risk of Parkinson's disease by blocking MAO-B which degrades dopamine to 6-Hydroxy-Dop. and liberates a hydroxide racical- which is sorta like micro quantities of sodium hydroxide- drain cleaner. Since this is happening is everyone's body all the time, slowly destroying your subsantia nigra or dopamine producing cells at a rate of anywhere from 4-12% per decade.
This progressive loss of dopamine cells is one reason why as people age their movements slow down, their emotions flatten a bit, they're less likely to try new things etc...A good deal of this looks preventable with nicotine or any MAO-B inhibitor. So MAO-B inhibition over decades may end up helping you maintain your capacity for pleasure, feel & think younger.


Nicotine has essentially 2 negative effects:

its primary metabolite nornicotine permanently reacts with or covalently binds to all sorts of different proteins in your body rendering them useless.
This effects does have one practical upshot though- among the proteins it reacts with *and neutralizes* are Beta-amyloid & hyperphosphorylated tau -- two neurotoxic proteins that cause Alzheimer's.

While Nicotine is beneficial for many parts of the brain it is selectively and potently neurotoxic to one part of the brain known as the fasciculus retroflexus. The FR is a pathway important in aspects of self control, addiction(Frontal lobe projects thru FR back to limbic sys. exacerbating loss of higher brain control of impulses) REM sleep(vital to learning), hippocampal function & goal directed behavior.
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Interesting. I've been smoking tobacco for about a year or two now. Gradually getting worse and addicted.

This could prove useful.
 
Mecamylamine and a nicotinic nootropic...sounds like a rediculous combination. Mecmylamine is a known memory impairing and stupifying drug, used in lab animal testing (uggh...not right) of potential nootropic agents as a standard memory/cognitive impairing drug.

Gah...tobacco....I smoke way too much. Perhaps, thinking about it, my memory and cognitive issues might be leading me to that, similar to how most schizos smoke, apparently, in a subconsciously-directed attempt to alleviate some of the cognitive dysfunction that so often attends schizoprenia. I too, had several nasty affairs with GBL, heavy, heavy use, got to me more than once, as did fullblown withdrawal....a really nasty affair, very unpleasant, I would say much much worse than opioid withdrawal, and even a fair bit worse than benzo withdrawal.

I haven't touched GHB/GBL, save for the use, shared, of perhaps 30ml, shared equally between three people, over time, during the last/past year, and will never touch the stuff again, but combined with my past barbiturate withdrawal (thinking combined effects on AMPA receptors, due to chronic antagonism possibly inducing a rebound hyperglutamatergic state, compounded with the same hyperexcitatory state thanks to the obvious lack of GABAergic activity) and still have major cognitive and memory dysfunction.

I think I'm going to go purchase some more huperzine-A, after trying it in the past to some good results (currently taking piracetam also).

After going to the shop and buying some more rolling baccy...uggh....
Nicotine patches I find don't stay on, although I guess I could do an extraction, and along with all the other forms of non-smoked administration, are incredibly pricy...way more than I can afford.

As for epibatidine analogs, yes, its been tried, and as far as I know, the result was always a potent paralysing neurotoxin. Its both a nicotinic agonist, and muscarinic antagonist, the latter at higher concentrations, although not very much higher, than its affinity for the NAChR. Not sure if it targets the M1 subtype present in the prefrontal cortex (proliferation of this subtype, apparently, is increased by piracetam), but if it does, that may to some extent, counter potential nootropic effects (think M1 inhibition by atropine, scopolamine, etc, and other nightshade/datura alkaloids)

Likely, at any rate, to be extremely complex, considered in an in-vivo human model. And of course, with the potential for extreme toxicity.
 
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