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The Big and Bangin' Pseudo-Advanced Drug Chemistry, Pharmacology and More Thread, V.2

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Cotcha Yankinov said:
Do antagonists/inverse agonists ever get close to increasing neural activity because the amount of auto receptors out number the regular receptors? It seems at some times a partial agonist can work as an antagonist because it's displacing a more efficacious ligand..
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To your second point, I'd say that it'd depend on some factors including concentration of the partial agonist (which results in the specific receptor saturation). The endogenous ligand is by definition a full agonist, and so assuming that all the receptors are saturated with endogenous ligands, introducing a partial agonist in necessary concentrations to achieve complete displacement of all the endogenous ligands to the receptor (we're of course assuming the partial agonist has a much higher affinity for the receptor so that displacement takes place easily) would mean that the overall response is reduced, and in that case the partial agonist would actually kind of be an antagonist (assuming the antagonist doesn't achieve full receptor saturation; if so, then by definition there would be 0 response overall; if partial saturation is achieved then only partial response is suppressed). As belligerent mentioned, this can happen if the "endogenous ligand" is something one continually administers in high concentrations (full mu opioid agonists).

But in most situations, I think the endogenous ligand is in concentrations such that most of the receptors are not occupied, and so introducing a partial agonist will bind to the unoccupied receptors (and occupied ones if the affinity is high enough) will result in an overall increased response.
 
aced126 said:
But in most situations, I think the endogenous ligand is in concentrations such that most of the receptors are not occupied, and so introducing a partial agonist will bind to the unoccupied receptors (and occupied ones if the affinity is high enough) will result in an overall increased response.
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As far as I know that's true, most partial agonists I've heard of do produce an agonist-like effect rather than the opposite in an individual who hasn't taken anything for a while. If I'm not mistaken THC (what about other major cannabinoids?) is also a partial agonist.
 
aced126 said:
Is 2-benzylpiperidine a reuptake blocker only though? It could very well act as a releasing agent. For desoxypipradol the phenyl ring could in some ways act as a bioisostere for the carbomethoxy group?
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i mentioned it based on the assumption that MPH itself isn't a reuptake blocker only, from that study dopa posted a while ago proposing 'transporter inverse agonism'. MPH and coke are very different than bupropion
 
Why hasn't

(1R,2S)-1-methoxy-2-methylamino-1-phenylpropane.png


O-METHYL EPHEDRA

been explored yet? Or has it been? I realize it might be expected to be a nerve racking adrenergic high, but you never know, and its synthesis from ephedra appears to me to be facile.
 
I suggested that a while a go. It should technically have decent dopaminergic activity. O-demethylation will reduce BBB penetration and increase affinity for adrenergic receptors around the body and heart. That's why I suspect it won't be that great.
 
Know technique to make from a wizard of a master of bakin' flash methods and in around 8 mins (I personally know this works) and out of sudafed pe to make Seth-or- D methMethamphetamine or D Meth-methamphetamine in 8 minutes with and one chemicals/ 2 products at chemist with just a microwave and electric stove and metal pan with water. I guarantee and done research into this myself and apart from microwave (tricky)lol you'll know why when I say the need of chemical and water to super fused to be heated adding two products to heat at a half max if that but getting a bit to fusr two more times and then smell the wizadry methamphetamine exactly like the true pseudeo gear fruity smell chemical 'yet still' fruity and will if anyones interested help explainr how to.from Sudafed PE to ????wizadry D Seth Methamphetamine? ?
 
basically if you can bake a cake, you can make MA
but we do not discuss synthesis here
however the level of coherence in the above post suggests the MA has already been made and consumed, however
 
Sometimes methoxies are quite metabolically resistant, for example on the 2Cx's and DOx's.
 
True, although I think phenyl methoxies are more metabolically stable than just alkyl methoxies.
 
Why is it that way though? You'd think that an aromatic -oxy group would be a better leaving group than an aliphatic one.
 
It's an ether. They are quite strong. Anyway, why can't this molecule

1-(3,4-dihydroxyphenyl)-2-methylaminoethane.png


be used as a false neurotransmitter? (Perhaps "improved NT" would be a better name for it.) Why don't our bodies produce this N-methyl-DA on their own already? Too pleasurable?
 
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Yes Belligerent, however I think that protonation on the oxygen occurs first before leaving, which in that case phenyl methoxies would be less labile than aliphatics; it is harder for the phenyl methoxy to be protonated due to pi delocalisation of a lone pair.
 
generally speaking ethers are awful leaving groups, aromatic or aliphatic

also N-methyl dopamine i'd bet can be used as a surrogate for dopamine, but good luck getting it past the BBB
 
Could you extend it with a methylene so that you get:

3-Amino-4-(3%2C4-dihydroxyphenyl)butanoic%20acid.png


3-Amino-4-(3,4-dihydroxyphenyl)butanoic acid

to still get it through the BBB with LAT and have it decarboxylated to N-methyl dopamine, or do you suppose it would not be 'recognized' well enough to bind? (i.e. does LAT only transport alpha amino acids or also beta?)
 
i.e. does LAT only transport alpha amino acids
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I would suspect that's the case, even if LAT moves them past BBB there is the issue of them being recognized at L-amino acid decarboxylases.
 
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sekio said:
generally speaking ethers are awful leaving groups, aromatic or aliphatic

also N-methyl dopamine i'd bet can be used as a surrogate for dopamine, but good luck getting it past the BBB
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I'd wager this molecule

1-(3,4-diacetoxyphenyl)-2-methylaminoethane.png


would cross the blood brain barrier intravenously.
 
Sure, if it weren't going to be rapidly deacetylated....
 
Yes, but that's what the intravenous administration is for. For example, IV heroin (diacetylmorphine) gets past the BBB 3x better than morphine.
 
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