N&PD Moderators: Skorpio
Would replacing hydrogen with deuterium change the effects of a drug?
Something I've been wondering about... I know that hydrogen and deuterium differ by mass and thus can exhibit slight differences in chemical reactions (for example drinking only D2O will kill you eventually.
So would changing all the hydrogen in (for example) lsd affect it's effects enough to be noticable?
Shouldn't change the effects per say, but in general may change the pharmacokinetics, such as higher BA/longer half-life which may mean you can have the same effects with lower doses or a longer duration of action. Have no idea what the results would be for lsd specifically.
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BallsStapledToLeg
Greenlighter
Surprisingly some drugs actually do have different affinities if some hydrogens are replaced with isotopes. I remember there was a bit of a row a couple years back when a company basically did that to try and extend the patent on an anti psychotic they owned.
http://pipeline.corante.com/archives/2013/05/07/an_update_on_deuterium_drugs.php
Very interesting, perhaps someone should try making deuterium versions of the more common drugs, so we won't have to guess 
From http://www.concertpharma.com/research/#CTP499 which is found on the page from the link in your post.
"Because deuterium forms more stable bonds with carbon, deuterium substitution can in some cases alter
drug metabolism, including through improved metabolic stability, reduced formation of toxic
metabolites, increased formation of desired active metabolites, or a combination of these effects. At the
same time, because deuterium closely resembles hydrogen, the substitution of deuterium for hydrogen
has generally been found not to materially alter the intrinsic biological activity of a compound.
Deuterated compounds can generally be expected to retain biochemical potency and selectivity similar to
their hydrogen analogs."
Replacing an H with a D might turn drugs that aren't viable because they have to be injected every 2 hours/have toxic metabolites with horrible side effects into medications that can be taken orally once a day with a better safety profile then the results of taking said drug may be different, but analog to analog at equal serum levels the effects shouldn't be any different.
Maybe a deuterated analog of DMT could be taken orally without an MAO inhibitor and still be active for example(I don't know enough about MAO to venture a guess), but it shouldn't feel any different than regular DMT.
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Folley
Bluelighter
Aren't you basically just talking about an analogue?
BallsStapledToLeg
Greenlighter
Very strange they should mention that, there are tons of examples in the literature of deuterated drugs having different affinities. In fact its a big problem when doing binding assays as the radiolabeled drugs often display slightly different affinities than the non-radiolabeled ones which can make some of the calculations much more complicated.
If you were curious about the effects of deuteration on amphetamines here's a great study on it:
http://www.ncbi.nlm.nih.gov/pubmed/21219698
sekio
Bluelight Crew
Unless the deuterium is in a spot where it is liable to get metabolised (c.f. kinetic isotope effect) it shouldn't play much of a role in altering the effects of a drug.
babylonboy
Bluelighter
Well, a very specific type of analogue. "Analogue" can mean a drug that is structurally or functionally similar to another in any way. It's a broad term, and not a very deep way to understand these relationships. Deuterium is an isotope of hydrogen, which means it is the same element, because it has the same number of protons (1) in its nucleus, which is what makes an atom of an element an atom of that element and not of another. Common hydrogen (known as protium if you need to distinguish between it and a heavier isotope, which you almost never do) has a single proton (positive) as its nucleus, orbited by a single electron (negative) (when it's electrically balanced, which we'll assume it is). Deuterium has one proton, one electron, and also a neutral particle in its nucleus, a neutron. Neutrons are electrically neutral, but they have mass (hence H2O in which the hydrogen atoms are the deuterium isotope being called "heavy water"). So, normally, an analogue will have methyl group (a carbon with three hydrogens bonded to it) in place of a hydrogen, or perhaps a fluorine atom instead. These are pretty similar, but nothing like as similar two molecules that differ only by a single neutron. So, take MDMA. If you replaced one of the protium atoms with a deuterium atom, it still has the same structure, the same number of the same kind of molecules in the same structure with the same charge, except one of those tiny insignificant little hydrogen atoms, the smallest atoms of all, the ones that are so small we don't even usually draw them in a skeletal formula, just one of those has an extra little particle that is way, way smaller than a single atom at its core. So, no, 2C-E is an analogue of mescaline, two molecules that differ only by the replacement of one protium atom with a deuterum atom are so incredibly closely related that I cannot conceive of a way two chemicals could be more similar, and don't even have a word for such a relationship.
tryp2fun
Bluelighter
Incunabula
Bluelighter
babylonboy
Bluelighter
What a gorgeous word. Thank you.
What exactly are you extrapolating from SPE cartridges to human receptors? And having a different number of protons or electrons is a whole lot different than having an extra neutron when it comes to affinity/efficacy in vivo...
BallsStapledToLeg
Greenlighter
All I was trying to show there was that affinity differences do exist between deuterated compounds and their parent compounds. No SPE cartridges arent neurons, but the basic principle is the same
ebola?
Bluelight Crew
Not really. In some sense, it is the same compound. For example, in a compound containing 'naturally found' hydrogen, there will be a small proportion of deuterium atoms in addition to the much more common H1 isotope.
ebola
babylonboy
Bluelighter
I presume that Folley did not understand what a deuterium atom is, and thought it was a heavier atom that could be substituted to a position much in the way a halogen might be. You are right, of course, and your point raises what I think is an interesting corollary to the OPs question? Would removing all the molecules in which deuterium is present from a sample of a drug change the effects?
atara
Bluelighter
Next up: 2,2-dideutera-benzodioxole analogs of popular empathogens.
Additionally, deuterium atoms hydrogen bond differently. This means that replacing protium on an amino or hydroxy function is one of the most likely places to significantly alter pharmacology.
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sekio
Bluelight Crew
They also undergo exhanges in protic solvents, IIRC. So, being mostly made of water, the alcohol groups would not stay deuterated in the body.