Would replacing hydrogen with deuterium change the effects of a drug?

[tryp2fun]

Hasn't anyone else seen this?

Psychopharmacology (Berl). 2012 Jun;221(4):709-18. doi: 10.1007/s00213-011-2616-6. Epub 2012 Jan 6.
Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor.
Halberstadt AL, Nichols DE, Geyer MA.
Author information
Abstract
RATIONALE:

Ayahuasca is a psychoactive tea prepared from a combination of plants that contain a hallucinogenic tryptamine and monoamine oxidase inhibitors (MAOIs). Behavioral pattern monitor (BPM) experiments demonstrated that the combination of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and a behaviorally inactive dose of an MAO(A) inhibitor such as harmaline or clorgyline induces biphasic effects on locomotor activity in rats, initially reducing locomotion and then increasing activity as time progresses.
OBJECTIVES:

The present study investigated whether the biphasic locomotor profile induced by the combination of 5-MeO-DMT and an MAOI is a consequence of a reduction in the rate of 5-MeO-DMT metabolism. This hypothesis was tested using a deuterated derivative of 5-MeO-DMT (α,α,β,β-tetradeutero-5-MeO-DMT) that is resistant to metabolism by MAO.
RESULTS:

Confirming our previous findings, 1.0 mg/kg 5-MeO-DMT (s.c.) had biphasic effects on locomotor activity in rats pretreated with a behaviorally inactive dose of the nonselective MAOI pargyline (10 mg/kg). Administration of 5-MeO-DMT alone, even at doses greater than 1.0 mg/kg, produced only reductions in locomotor activity. Although low doses of α,α,β,β-tetradeutero-5-MeO-DMT (0.3 and 1.0 mg/kg, s.c.) produced only hypoactivity in the BPM, a dose of 3.0 mg/kg induced a biphasic locomotor profile similar to that produced by the combination of 5-MeO-DMT and an MAOI. Receptor binding studies demonstrated that deuterium substitution had little effect on the affinity of 5-MeO-DMT for a wide variety of neurotransmitter binding sites.
CONCLUSIONS:

The finding with α,α,β,β-tetradeutero-5-MeO-DMT indicates that the hyperactivity induced by 5-MeO-DMT after MAO inhibition is a consequence of reduced metabolism of 5-MeO-DMT, leading to prolonged occupation of central serotonin receptors. These results demonstrate that deuterated tryptamines may be useful in behavioral and pharmacological studies to mimic the effects of tryptamine/MAOI combinations.

 

[babylonboy]

There is nothing new under the sun.

 

[babylonboy]

Sorry for double post, but legit new info; I just happened across a paper that discusses the synthesis of deuterated methaqualone, PCP, methamphetamine and DOM. The purpose of these being made was so they could be identified at low concentrations in body fluids, so presumably they were at some point assayed in vivo, though perhaps only in rats.

 

[endotropic]

Sorry for double post, but legit new info; I just happened across a paper that discusses the synthesis of deuterated methaqualone, PCP, methamphetamine and DOM. The purpose of these being made was so they could be identified at low concentrations in body fluids, so presumably they were at some point assayed in vivo, though perhaps only in rats.

Could I get a link to that paper? I'm interested to see how they detected the deuterium.

 

[Folley]

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.

What a fantastic explanation for something that otherwise would have gone completely over my head. Props for that, shame I didn't see it before

 

[babylonboy]

I can only hope your comment is in earnest. If you genuinely expressing gratitude for my explanation of the subject, then you are more than welcome. Most people find it boring, if you have found what I have to say enjoyable and informative, then you are more than welcome.

 

[Refluxer]

Some people produced deuteriated amphetamine in Sweden sometime in the 90's, trying to circumvent illegality. They were busted and the deuteriated version was judged to be so similar it was as illegal as non-deuteriated amphetamine.

 

[hyperdimension]

Could I get a link to that paper? I'm interested to see how they detected the deuterium.

I would imagine with mass spectrometry. The deuterated compound(s) would have molecular ions/fragments containing deuterium with masses greater (by the number of deuterium atoms present) than their non-deuterated counterparts.

I know that MS will differentiate between isotopologues (thanks for the word, tryp2fun), but I would imagine that GC wouldn't, because the compounds would be so similar chemically. Feel free to correct me on that, though.

(edit: not used to seeing date/month in this order. sorry for bumping an old post.)

 

[endotropic]

I would imagine with mass spectrometry. The deuterated compound(s) would have molecular ions/fragments containing deuterium with masses greater (by the number of deuterium atoms present) than their non-deuterated counterparts.

I know that MS will differentiate between isotopologues (thanks for the word, tryp2fun), but I would imagine that GC wouldn't, because the compounds would be so similar chemically. Feel free to correct me on that, though.

(edit: not used to seeing date/month in this order. sorry for bumping an old post.)

No problem on the bump, this thread isn't so old that I don't remember the topic yet

I think you're right about the MS for the detection. I was hoping it was something simpler, along the lines of how you detect tritium, but for stable isotopes the weight is the only detectable difference.

 

[Limpet_Chicken]

Wouldn't deuterated analogs be legal in the UK?

I think the fascist drug war soldiers here might well have created a loophole by outlawing en-masse, PIHKAL/TIHKAL compounds.
Thus some deutero-analogs of drugs are specifically listed, inferring, by omission, that those left unscheduled, with our lack of an analog act, all the rest.

 

[Crystal Alchemist]

Wouldn't deuterated analogs be legal in the UK?

I think the fascist drug war soldiers here might well have created a loophole by outlawing en-masse, PIHKAL/TIHKAL compounds.
Thus some deutero-analogs of drugs are specifically listed, inferring, by omission, that those left unscheduled, with our lack of an analog act, all the rest.

Based on Refluxer's post it doesn't sound very promising.

Some people produced deuteriated amphetamine in Sweden sometime in the 90's, trying to circumvent illegality. They were busted and the deuteriated version was judged to be so similar it was as illegal as non-deuteriated amphetamine.

And babylonboy, I found your explanation to be very straightforward and informative and I appreciate your efforts to help further educate us