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> Acedemic Exercise: Make A Pill
Tone
post Feb 13, 2009, 10:21 AM
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If you could make up a hypothetical pill complex for better mood and wellbeing, what would you make? think it up and post it. First you post what is in it, then a few sentences of notes about it under that. here is an example:

----

Each 570 mg pill contains

3 Micrograms Naltrexone
3 Milligrams Naloxone
5 Milligrams Hydrocodone
5 Milligrams Hydromorphone
5 Milligrams Bioperine Piperine
50 Milligrams Tianeptine
50 Milligrams Siliphos Silymarin Phytosome
50 Milligrams Rutin
50 Milligrams trans-Resveratol HCl
50 Milligrams R-alpha-Lipoic acid tromethamine
50 Milligrams Pine Bark Extract 95% OPC
250 Milligrams Calcium Ascorbate


Explanation: This pill its taken 4 times per day. Piperine causes a little more absorbency from the gut. Studies were done with oral Naloxone with opioids. When Oral, Nalxone but not Naltrexone is very weak and poorly absorbed, not to mention what little does make it into the blood is rapidly destroyed within 90 minutes. Ultra Low dose Naltrexone and Oral Naloxone are what little tolerance fighters we have.

The other primary actives are the opioid complex and Tianeptine which is Stablon. These two go together extremely well.

Lipoic Acid and Vitamin C are as salts to be more stable not so acidic and not interfere with the other ingredients. trans-Resveratrol as salt to be more stable and possibly absorb better. This is novel compared to what is normally available with those.

The antioxidants are not just brain protective, but have a mild psychoactive effect thats just above the threshold of noticeable, especially resveratrol and Vitamin C, although it may take 2000 mg + of vitamin C to get its weak psychoactive effect, but that wouldnt fit into a pill and would have to be taken separately.
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Hey Hey
post Feb 13, 2009, 09:12 PM
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QUOTE(Tone @ Feb 13, 2009, 06:21 PM) *
Lipoic Acid and Vitamin C are as salts to be more stable not so acidic and not interfere with the other ingredients. trans-Resveratrol as salt to be more stable and possibly absorb better. This is novel compared to what is normally available with those.
Interesting and thoughtful approach.

Unless you propose an enteric coating, then the salts will experience a very low pH in the stomach and dissociation could invalidate the need for your various salt forms. I'm not sure where the best location is for absorption of the various ingredients without checking on them (pH is one of the important factors in determining the extent and rate of absorption), but with an enteric coat (depends on the thickness and type) transit through beyond the stomach would occur for dissolution as pH increases. Also, the combination of various ingredients is a complex process, as interactions (pharmacologically, chemically, toxicologically etc) can occur that could inactivate, reduce or increase the expected potency, cause precipitations, gas production, local inflammation, etc, etc.

So in vitro investigations followed by cell/tissue studies, animal studies and human trials would be required, to determine, not least, any changes needed in the dosage of the individual components to give the desired effect, adverse effects, and so on. Maybe the size of the dose should also be considered. With the usual typical adjuncts (e.g. sweeteners, binders etc) it might only be suitable for a horse to swallow at the split (q.i.d.) you suggest. Also, consider the range of oral formulations (solid, liquid, tablet, capsule etc). Quite a task ahead then, although there might be some possible shortcuts if there is present evidence for combinations already used. Better get started ...

I'm sure experts on the board will be able to demonstrate their expertise in pharmacology, pharmacodynamics, pharmacodynamics, physical pharmaceutics, toxicology, etc, and make recommendations as to how to set about the design of this new formulation.

A nice fizzy formulation here:

http://www.freepatentsonline.com/6261589.html
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shibireru
post Feb 13, 2009, 11:04 PM
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How interesting! I undertook this very task earlier today and my list had a few of the same ingredients! Here's mine:

(This is purely hypothetical since some of these substances won't pass through the blood brain barrier and others won't make it as far as the bloodstream.)

Hydromorphone hydrochloride
DAMGO
Tianeptine
Bergamottin
Piperine
Ibudilast/Rolipram/Mesembrine (from sceletium tortuosum) (phosphodiesterase 4 inhibitors)
Proglumide
7-Nitroindazole
J-113397 (Nociceptin receptor-1 antagonist)
Domperidone
Dextroamphetamine
Memantine
Magnesium
Clonidine/Dexmedetomidine/Tizanidine
L-Arginine
Bremelanotide
Cabergoline
Forskolin
Inositol
Testosterone
Anastrozole
Glial cell line-derived neurotrophic factor
Brain derived neurotrophic factor
Insulin-like growth factor-1
Cypin and tubulin
HU-308 (Cannabinoid 2 receptor agonist)
Agomelatine


This might be fatal through respiratory depression... It might also cause a stroke. And the cyp3a4 inhibitors bergamottin and piperine might result in a decrease of efficacy for a number of the substances on the list.

The DAMGO, Proglumide, J-113397, phosphodiesterase 4 inhibitor, and 7-nitroindazole are there to attenuate, or preclude downregulation of MOPrs, or, rather, tolerance ot opiods (since tolerance often occurs in absence of downregulation of MOPRs).
DAMGO, to be specific, has been shown to occasion endocytosis of MOPRs when administered with morphine and morphine-like substances, whereas these substances by themselves do not, but merely decrease the sensitivity of the MOPRs presumably through protein kinase a-mediated phosphorylation of the receptor protein residues where the heterotrimeric g protein binds. One might think this to be a bad thing but by the time they reemerge from the cytosol they've been recycled and resensitized, or so a study has claimed.
The domperidone is for nausea.
The alpha 2 adrenergic receptor agonist is there to reduce the sympathomimetic effects (tachycardia, hypertension, etc...) of the dextroamphetamine and to increase the potency of the hydromorphone.
The L-arginine is included for its vasodilating properties - to counteract the effects of the dextroamphetamine and increase blood flow to the genitalia.
The memantine and magnesium are partial nmda antagonists which are there to slow the development of tolerance to the dextroamphetamine.
Bremelanotide increases libido and strength of erections.
The cabergoline, a DA2r agonist, decreases prolactin levels and thereby increases libido.
Forskolin directly activates adenylate cyclase, increasing cyclic adenosine monophosphate production out of proportion with activation of the receptors of the relevant neuron, and in so doing somehow produces upregulation (through increase of quantity and sensitivity) of D2 receptors in certain brain regions
The inositol achieves the same thing as the Forskolin but by different mechanisms.
The anastrozole decreases the rate of conversion of testosterone to oestrogens
The glial cell line-derived neurotrophic factor increases growth rate in at least one of the pleasure centers of the brain (the ventral globus pallidus, I believe)
Cypin and tublin work together to create new dendrites and synapses
HU-308 is a Cannabinoid 2 receptor agonist, which has been shown to be neuroprotective and promote neurogenesis
Agomelatine is a potent melatonin 1 and melatonin 2 receptor agonist as well as antagonist of the 5-HT2C receptor
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Tone
post Feb 14, 2009, 01:16 PM
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Naloxone is an injection drug, never used orally. Some people got the idea to try the poorly absorbed, rapidly destroyed antagonist orally for opioid constipation:

http://www.meb.uni-bonn.de/cgi-bin/mycite?...f=MEDL/96271156


These people actually didnt have much trouble with higher doses of Naloxone (not to be confused with naltrexone which lasts 25+ times longer) . These experiments showed the researchers that the use of 5 mg to begin with is called for to avoid trouble. So if you go by their experience and be more conservative, below even that might be useful along with Ultra Low Dose Naltrexone, say 0.25 mg to 3 mg, maybe closer to the low end.
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Tone
post Feb 14, 2009, 01:24 PM
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QUOTE(Hey Hey @ Feb 13, 2009, 11:12 PM) *

QUOTE(Tone @ Feb 13, 2009, 06:21 PM) *
Lipoic Acid and Vitamin C are as salts to be more stable not so acidic and not interfere with the other ingredients. trans-Resveratrol as salt to be more stable and possibly absorb better. This is novel compared to what is normally available with those.
Interesting and thoughtful approach.

Unless you propose an enteric coating, then the salts will experience a very low pH in the stomach and dissociation could invalidate the need for your various salt forms. I'm not sure where the best location is for absorption of the various ingredients without checking on them (pH is one of the important factors in determining the extent and rate of absorption), but with an enteric coat (depends on the thickness and type) transit through beyond the stomach would occur for dissolution as pH increases. Also, the combination of various ingredients is a complex process, as interactions (pharmacologically, chemically, toxicologically etc) can occur that could inactivate, reduce or increase the expected potency, cause precipitations, gas production, local inflammation, etc, etc.

So in vitro investigations followed by cell/tissue studies, animal studies and human trials would be required, to determine, not least, any changes needed in the dosage of the individual components to give the desired effect, adverse effects, and so on. Maybe the size of the dose should also be considered. With the usual typical adjuncts (e.g. sweeteners, binders etc) it might only be suitable for a horse to swallow at the split (q.i.d.) you suggest. Also, consider the range of oral formulations (solid, liquid, tablet, capsule etc). Quite a task ahead then, although there might be some possible shortcuts if there is present evidence for combinations already used. Better get started ...

I'm sure experts on the board will be able to demonstrate their expertise in pharmacology, pharmacodynamics, pharmacodynamics, physical pharmaceutics, toxicology, etc, and make recommendations as to how to set about the design of this new formulation.

A nice fizzy formulation here:

http://www.freepatentsonline.com/6261589.html



also notice R-lipoic acid is better than SR mixture

for that drink, i wouldnt include copper in it, unless it was a mere 5% the RDA of copper, 100 micrograms. copper is best in low doses, its like iron, a free radical maker when you get too much

also i want add that O-Desmethyltramadol, the metabolite that forms SLOWLY and in limited amounts from taking tramadol, may be the ultimate opioid, we dont know because theres never been a pill of it, but if tramadol is rivaling vicodin and so good to people with high CYP2D6, imagine how its active metabolite in a pill would be.

http://upload.wikimedia.org/wikipedia/en/4...hyltramadol.png
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astroidea
post Apr 09, 2011, 12:48 AM
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A big delicious balanced nutritious meal
Amphetamine
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orangesand
post May 23, 2011, 10:19 AM
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QUOTE(astroidea @ Apr 09, 2011, 04:48 AM) *

A big delicious balanced nutritious meal
Amphetamine


Cheers!(Take out the amphetamine)
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