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resorcinol
05-04-2009, 12:49 AM
radioactive.

We'll never, ever know what 2C-At would feel like, or DOAt. If the SAR trend were to continue 2C-At would be very potent. It would also be very potent at tearing your 5-ht(2a) receptors to shreds with radiation (and plenty of other cells also). In fact ingesting a mg of 2C-At would kill you dead. It's so sad that At is radioactive.

We can approximate though. The radius of the trifluoromethane group is similar to the atomic radius of astatine, and TFM is a pseudohalogen. So 2C-TFM (which is very potent) is probably a good representation of how 2C-At would feel if At wasn't radioactive.

There are interesting heteroatoms that do have stable isotopes that can be used to create exotic drugs, though. Selenium is the one with perhaps the largest untapped potential. It's a chalcogen just like oxygen and sulfur, and we know that chalcogens (especially oxygen, and occasionally sulfur) are incorporated into many psychoactive drugs. Selenium could almost certainly substitute for oxygen or sulfur in MANY psychoactives and result in active drugs. 2C-Se (which actually has a methylseleno group at position 4 since selenium forms two covalent bonds, not one like a halogen). 2C-Se is a fullblown hallucinogen of the classical type at 100 mg (not very potent, but definitely active and worthwhile, unlike the flop that was 2C-N). 2C-Se-x (the selenium analogs of the sulfur containing 2C-T-x drugs) drugs would likely be interesting and potent, as would DOSe (which would likely be quite potent).

I've lately had a fascination with morphine-like opioids where some of the oxygens are replaced with either sulfur or selenium ... a place where few opioids have gone to actual human use (sulfur has in a few rare cases like sufentanil and dimethylthiambutene, but selenium hasn't). I'm pretty sure that 14-mercapto-hydrocodone (imagine oxycodone but replace the oxygen in the -OH at position 14 with a -SH), 14-methylthio-hydrocodone (imagine oxycodone but replace that same -OH as before with a -S-CH3), and 14-methylseleno-hydrocodone (replace the same -OH as in the other two with a -Se-CH3) would all be awesome.

The 14-mercapto-hydrocodone would likely be similar in potency and effects to oxycodone. The latter two would likely be similar in effects to oxycodone but more potent (possibly by a significant margin).

So while we can never know what drugs with astatine, polonium, francium, etc heteroatoms would feel like because the elements are unstable, there are stable elements that have not been exploited very much in pharmacology (selenium is particularly attention grabbing because chalcogen atoms are ubiquitous in drugs, psychoactive and non ... oxygen is everywhere, sulfur is occasionally found, but selenium has been ignored [even though it's likely to create relatively non-toxic organic chalcogen containing compounds ... non toxic in that the selenium's presence is unlikely to impart toxic characteristics to most cases where it replaces oxygen or sulfur ... of course highly toxic compounds that contain selenium could be created, like an irreversible inhbitor of cholinesterase that contains selenium heteroatom(s) would be deadly, but not because of the selenium, but because of it's pharmacological action ... sarin is a cholinesterase inhibitor that's irreversible and that's how it kills]). Tellurium is an even heavier chalcogen than selenium (next down in the chalcogen column), but tellurium heteroatoms would be bad news -- there'd definitely be toxicity issues directly from tellurium. Polonium is the next chalcogen down, with an even heavier atomic mass, but whoops.... it's radioactive. I'm sure 14-methylpolono-hydrocodone is potentially a mu agonist, but the alpha particles from the radioactive decay of polonium would shred your mu receptors and plenty of other cells throughout the systemic circulation.... polonium is HIGHLY radiologically toxic when ingested (relatively safe outside the body though even in large quantities since alpha particles from alpha decay cannot penetrate into the body from an alpha emitter outside the body). So selenium, deserves some attention. Tellurium is rightfully ignored for chemical toxicity reasons, polonium because it's a highly toxic radiological poison.

30_Units
05-04-2009, 01:26 PM
I love your threads.

Uncle Wiggly
05-04-2009, 01:52 PM
I'm pretty ignorant when it comes to most chemistry. Is the Selenium you're writing about the same type of thing that's in my prescription shampoo? Selenium Sulfide .02%. Please excuse my extreme ignorance. Thanks in advance for any info.

Mayo
05-04-2009, 03:19 PM
thats very interesting resorcinol. But I don't agree, especially re oxygen:
Selenium could almost certainly substitute for oxygen or sulfur in MANY psychoactives and result in active drugs.

Chemically, Se and O have very different reactivities, despite them being in the same group.
Physiologically, they are treated very different as well. Just my opinion.
But oxygen is rather unique, a real degenerate... :p..Have you read much about oxygen chemistry?
Its pretty interesting. Like liquid oxygen being magnetic, how cool is that?

But you're great man, I always love reading your posts.
Chalcogens...heh...nice.

resorcinol
05-04-2009, 06:48 PM
I'm pretty ignorant when it comes to most chemistry. Is the Selenium you're writing about the same type of thing that's in my prescription shampoo? Selenium Sulfide .02%. Please excuse my extreme ignorance. Thanks in advance for any info.

Selenium is selenium, so yeah, that's the same selenium. It's just a different compound of selenium than the ones I was mentioning (much different in that selenium sulfide is inorganic while drugs are nearly always organic compounds). Pure elemental selenium is just Se.

thats very interesting resorcinol. But I don't agree, especially re oxygen:
Selenium could almost certainly substitute for oxygen or sulfur in MANY psychoactives and result in active drugs.

Chemically, Se and O have very different reactivities, despite them being in the same group.
Physiologically, they are treated very different as well. Just my opinion.
But oxygen is rather unique, a real degenerate... :p..Have you read much about oxygen chemistry?
Its pretty interesting. Like liquid oxygen being magnetic, how cool is that?

But you're great man, I always love reading your posts.
Chalcogens...heh...nice.

Definitely agree that oxygen and selenium have different reactivity -- and that oxygen is an oddity. Oxygen as you know exists in a triplet state of bonding between the two individual oxygen atoms in typical "air oxygen" or "diatomic oxygen" which renders it far less reactive than it would be in other forms. Even the metastable singlet form of diatomic oxygen is FAR more reactive ... in fact we need to input heat to get a fire going to convert some of the triplet state into singlet, which then oxidizes the organic material -- get enough heat output from the redox reaction now occurring to generate tons of singlet type O2 and the combustion becomes self sustaining (other oxygen radicals may be generated by the heat and contribute to sustained combustion also I believe ... you could maybe provide more info about that). Oxygen's triplet diatomic allotrope is para-freakin-magnetic, which is certainly odd (the singlet diatomic allotrope is DIAmagnetic though).

I wasn't really suggesting the degree of sameness between oxygen and sulfur or selenium that it may have come across as. I was more suggesting that it's pretty likely that having a selenium atom in a potential drug, where a known drug has an oxygen, would likely result in another active drug containing selenium (this is applicable ONLY where selenium could form the bonds of course, as there are some organic bonds to oxygen where selenium or even sulfur would not be stable or even not occur). Like, 14-methylseleno-hydrocodone would definitely be a stable compound. Methylseleno- groups are stable ways to add selenium heteroatoms to organic molecules. I also strongly suspect that the abovementioned -codone with selenium in it would be a mu agonist. Even if SAR is significantly different when changing out a O for Se, most of the fact that the above-mentioned drug is probably a mu agonist rests on the whole rest of the molecule and not the selenium part ... it would be very unlikely IMO that selenium would abolish mu opioid agonist activity. In fact, 14 substitution of -codones usually boosts activity, and I can't see why a methylseleno wouldn't boost it also. It's certainly not too big (selenium atom) as to create mu-receptor steric issues. It's similar enough to oxygen to use it as a "two bond" linker atom between two "parts" of an opioid -- having a nice long chain terminating in a phenyl ring of position 14 with these opioids creates super potent compounds when the chain and the main core of the phenanthrene opioid are "joined" by oxygen and its ability to form two covalent bonds -- I don't see any reason why selenium could not be used at that spot for the same purpose -- Se can form that kind of bond, it's just C-Se-C, which would work.

So I'm certainly not suggesting that selenium (nor sulfur) can just take the place of oxygen anywhere in any drug and be totally awesome or even possible, but that in some cases it could work and create quite novel psychoactive drugs.

For sulfur, what do you think about 14-mercapto-hydrocodone (the sulfur analog of oxycodone; -OH at 14 is replaced with -SH)? I know FOR SURE that replacing an -OH with an -SH does NOT always make another drug that is just as great as the -OH version (ethanol / booze is the perfect example actually .... the -OH ethanol is a GABA(A) agonist intoxicant and smells like a solvent but is palatable ... the -SH ethyl mercaptan is probably NOT a GABA(A) agonist and even if it was, ethyl mercaptan is one of the most disgusting smelling substances there is... it might be toxic also (don't know if it is for sure, I'd have to look it up). However, in this case, the -OH present in ethanol is a SIGNIFICANT part of the whole molecule ... the -OH is what makes simple short chain alcohols what they are, and it's what makes them probably behave as they do in the body. For ethanol, the -OH is indespensible.

I don't think the -OH is indespensible for oxycodone. Most of what oxycodone does including mu agonism in the body rests in its "core" phenanthrene/morphinan structure -- the -OH at 14 just boosts potency (oxycodone without that -OH is called hydrocodone. yall may have heard of it before :p ). So even loosing the -OH for just a plain old -H leaves us an active mu agonist. Since modifying the 14 substituent from -H to something else (and we're talking just small substituent groups here, no chains at the moment that totally alter the opioid and make 'em look more like fent in 3D space .... just small changes, like the -OH at 14 for oxycodone that gives it a little edge over the unsubstituted, -H at pos 14 hydrocodone). I believe that having a thiol group at 14 instead of a hydroxyl group would result in an active mu agonist. I believe it would be slightly more potent than hydrocodone but not enormously .... I tend to feel that any small substituent there would just add some potency ... especially I feel that the potency increase would be close to that of oxycodone over hydrocodone due to the analogous nature of the thiol group to the hydroxide group. Different chalcogen, but the activity as a mu agonist doesn't DEPEND on a particular chalcogen like the activity of booze does. I think the -SH 14 subbed hydrocodone would be quite similar to oxycodone in effects and potency.

Only one true way to know for sure.... synthesize some of that dope and drink a few mg down with some OJ! Robojunkie!..... we need a bioassay! :D

I'm agreeing though that oxygen differs from sulfur and selenium in many regards ... but also that there are similarities -- the periodic table is arranged this way for a reason of course.