4 ms·

Do you know of any examples where a racemic mixture has an effect dramatically different from what you'd expect from a combination of the enantiomers' effects?

kellerbw 7y ago
Thalidomide. One enantiomer is a great morning sickness drug, the other causes catastrophic birth defects.
- refurb 7y ago
  Thalidomide interconverts in the body. There is no difference between the enantiomers in the human body (there is in a petri dish).
tempguy9999 7y ago
I'm not sure I understand the question[0] fully but thalidomide? https://en.wikipedia.org/wiki/Thalidomide https://en.wikipedia.org/wiki/Thalidomide "Thalidomide is provided as a racemic mixture of two enantiomers; while there are reports that only one of the enantiomers may cause birth defects, the body converts each enantiomer into the other through mechanisms that are not well understood." [0] because a racemic mixture (https://en.wikipedia.org/wiki/Racemates https://en.wikipedia.org/wiki/Racemates) is a 50/50 mix of enantiomers: "In chemistry, a racemic mixture, or racemate [...] has equal amounts of left- and right-handed enantiomers of a chiral molecule" so if you took a racemic mixture surely you'd be getting a combination of the enantiomers' effects?
soulofmischief 7y ago
Amphetamine, for one. Levoamphetamine or dextroamphetamine provide two different physiological experiences (think coffee vs meth). The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself (the most common isomer found in amphetamine prescription products). From a perspective of safety, I don't have any reason to suspect esketamine to be any worse. However from a psychological perspective, we could be talking pretty big differences in some individuals where subtle changes in behavior or thought can have cascading effects on mood. But... that's why we're testing its efficacy, right? It's stupid not to try, and these test subjects are willing. One of the two isomers will be better in some categories. Could be that both together are the way to go. Having only encountered racemic ketamine I can definitely understand its uses in treating depression.
jazoom 7y ago
Commenters so far haven't actually answered your question. They just gave examples where the 2 enantiomers have different effects. There are countless examples of these since our bodies' molecules naturally have "handedness". What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. This is the real question here. For there to be a significant difference in this case one of the ketamine enantiomers would need to counteract the other's ill effects. Disclaimer: although I am a medical doctor, and my first University degree was in organic chemistry and biochemistry, some of this academic stuff is but a hazy memory for me.
- soulofmischief 7y ago
  > What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. I literally said: > The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself I did answer the question... exactly as OP asked. > For there to be a significant difference in this case one of the ketamine enantiomers would need to counteract the other's ill effects. This is precisely the case with amphetamine, where levoamphetamine is more relaxing and subtle and dextroamphetamine is much more physiologically demanding. A racemic mixture provides the perfect combination of effects whereas just dextroamphetamine by itself can be pretty rough on you. The difference in effect can be quite profound and drastically change your mood and behavior. I would know because I was force fed large amounts of amphetamines for my entire childhood. Name it and I've been prescribed to it.
  - jazoom 7y ago
    So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?
    - soulofmischief 7y ago
      > So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer? Is that the angle here? I thought we were comparing the total mass of each substance. OP asked about noticeable differences, not paradoxical effects. 25mg of dextro is obviously going to have a weaker overall effect than 50mg of racemic amp. But that's not what OP asked and it's not the context. The context is whether esketamine and racemic ketamine could provide a noticeably different experience. And the answer is yes. Just like amphetamine, the ketamine isomers have similar pharmacokinetic properties but not necessarily similarly pharmacodynamic properties.

kellerbw 7y ago

Thalidomide. One enantiomer is a great morning sickness drug, the other causes catastrophic birth defects.

refurb 7y ago
Thalidomide interconverts in the body. There is no difference between the enantiomers in the human body (there is in a petri dish).

tempguy9999 7y ago

I'm not sure I understand the question[0] fully but thalidomide? https://en.wikipedia.org/wiki/Thalidomide https://en.wikipedia.org/wiki/Thalidomide "Thalidomide is provided as a racemic mixture of two enantiomers; while there are reports that only one of the enantiomers may cause birth defects, the body converts each enantiomer into the other through mechanisms that are not well understood." [0] because a racemic mixture (https://en.wikipedia.org/wiki/Racemates https://en.wikipedia.org/wiki/Racemates) is a 50/50 mix of enantiomers: "In chemistry, a racemic mixture, or racemate [...] has equal amounts of left- and right-handed enantiomers of a chiral molecule" so if you took a racemic mixture surely you'd be getting a combination of the enantiomers' effects?

soulofmischief 7y ago

Amphetamine, for one. Levoamphetamine or dextroamphetamine provide two different physiological experiences (think coffee vs meth). The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself (the most common isomer found in amphetamine prescription products). From a perspective of safety, I don't have any reason to suspect esketamine to be any worse. However from a psychological perspective, we could be talking pretty big differences in some individuals where subtle changes in behavior or thought can have cascading effects on mood. But... that's why we're testing its efficacy, right? It's stupid not to try, and these test subjects are willing. One of the two isomers will be better in some categories. Could be that both together are the way to go. Having only encountered racemic ketamine I can definitely understand its uses in treating depression.

jazoom 7y ago

Commenters so far haven't actually answered your question. They just gave examples where the 2 enantiomers have different effects. There are countless examples of these since our bodies' molecules naturally have "handedness". What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. This is the real question here. For there to be a significant difference in this case one of the ketamine enantiomers would need to counteract the other's ill effects. Disclaimer: although I am a medical doctor, and my first University degree was in organic chemistry and biochemistry, some of this academic stuff is but a hazy memory for me.

soulofmischief 7y ago
> What you were essentially asking was would 100% of the "bad" enantiomer be significantly worse than a 50/50 mixture. I literally said: > The effects profile of racemic amphetamine is markedly different and much easier to handle physiologically than just dextroamphetamine by itself I did answer the question... exactly as OP asked. > For there to be a significant difference in this case one of the ketamine enantiomers would need to counteract the other's ill effects. This is precisely the case with amphetamine, where levoamphetamine is more relaxing and subtle and dextroamphetamine is much more physiologically demanding. A racemic mixture provides the perfect combination of effects whereas just dextroamphetamine by itself can be pretty rough on you. The difference in effect can be quite profound and drastically change your mood and behavior. I would know because I was force fed large amounts of amphetamines for my entire childhood. Name it and I've been prescribed to it.
- jazoom 7y ago
  So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?
  - soulofmischief 7y ago
    > So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer? Is that the angle here? I thought we were comparing the total mass of each substance. OP asked about noticeable differences, not paradoxical effects. 25mg of dextro is obviously going to have a weaker overall effect than 50mg of racemic amp. But that's not what OP asked and it's not the context. The context is whether esketamine and racemic ketamine could provide a noticeably different experience. And the answer is yes. Just like amphetamine, the ketamine isomers have similar pharmacokinetic properties but not necessarily similarly pharmacodynamic properties.