5 ms·

> it's a enantiomer of ketamine, it's literally 50% of the molecules in ketamine I’m not a biologist or a chemist. Why does this imply the chemical is as safe?

> it's a enantiomer of ketamine, it's literally 50% of the molecules in ketamine I’m not a biologist or a chemist. Why does this imply the chemical is as safe? What is the benefit? It seems like a blatant patent grab to bypass the low profit margins of ketamine. Is there evidence otherwise?

badamp 7y ago
The short answer is it can be both (ie safe, beneficial and effectively a patent grab). It is also unlikely that an enantiopure chemical is less safe then it’s racemic counterpart and not unlikely that it is beneficial (this is not without precedent... this is also chemistry 101 and I don’t feel this is the forum for it)... The doubt is not so much the safety but is the benefit of the enantiopure version worth the cost.
- tempguy9999 7y ago
  Per my comment above, thalidomide is a clear exception. This stands even if the chirality changes within the body.
  - rocqua 7y ago
    That was an example on the other direction. A pure chirality was safe, but a racemic mixture was dangerous. Here we know the racemic mixture is safe, which strongly suggests that either chirality in isolation is also safe.
    - Nasrudith 7y ago
      And to make in the previous worse it would apparently "autobalance" and flip to chirality which meant that even if they 100% isolated it at great expense is why we never saw "rebranded Thalimoide but isolated to be all morning sickness drug no birth defects". I don't know enough details to tell how long it took and if it could even be used safely under ludicrously impractical assumptions like "if you it freshly isolated in bulk and take it within five seconds it would be safe but expire in an hour".
      - tempguy9999 7y ago
        I think it flipped when in the body, so however long the shelf life was, it still wouldn't matter. Incidentally, and AIUI, the body has a tagging system for unwanted proteins. Once tagged, the proteins are removed. Thalidomide tagged the proteins the were specific to embryonic limb formation, and the body duly cleared them, leading to the infamous result. Again AIUI.
skissane 7y ago
Not a biologist or chemist either, but I'll try to give my layperson understanding: basically, many molecules exist in two different versions which are mirror images of each other (enantiomers). Most drugs are actually an equal mixture of both enantiomers (called a racemic mixture), but often only one of the enantiomers has the desired drug effect, and the other doesn't actually do anything. It is possible to create a drug which has only the effective enantiomer; usually, a pure dose of the effective enantiomer will be effective at half the dose as the racemic mixture. Medically, there are some advantages – both forms need to be metabolised by the liver, so being able to use half the dose to get the same effect gives the liver less work to do, which can reduce the risk of drug-induced liver injury. If the racemic mixture is already being widely used, then the risk of the pure effective enantiomer is likely to be low, since it is basically just a more effective form of the already used drug, and the side effect profile should be similar to the existing drug. Chemically, the manufacturing process is more complex, which adds to manufacturing costs; however, the main driver of additional costs is that you can get a new patent for the active enantiomer even after the patent on the racemic mixture is expired. For example, the common SSRI anti-depressant citalopram is the racemic mixture, whereas escitalopram is the S-enantiomer. Similarly, esketamine would be the S-enantiomer of ketamine.

badamp 7y ago

The short answer is it can be both (ie safe, beneficial and effectively a patent grab). It is also unlikely that an enantiopure chemical is less safe then it’s racemic counterpart and not unlikely that it is beneficial (this is not without precedent... this is also chemistry 101 and I don’t feel this is the forum for it)... The doubt is not so much the safety but is the benefit of the enantiopure version worth the cost.

tempguy9999 7y ago
Per my comment above, thalidomide is a clear exception. This stands even if the chirality changes within the body.
- rocqua 7y ago
  That was an example on the other direction. A pure chirality was safe, but a racemic mixture was dangerous. Here we know the racemic mixture is safe, which strongly suggests that either chirality in isolation is also safe.
  - Nasrudith 7y ago
    And to make in the previous worse it would apparently "autobalance" and flip to chirality which meant that even if they 100% isolated it at great expense is why we never saw "rebranded Thalimoide but isolated to be all morning sickness drug no birth defects". I don't know enough details to tell how long it took and if it could even be used safely under ludicrously impractical assumptions like "if you it freshly isolated in bulk and take it within five seconds it would be safe but expire in an hour".
    - tempguy9999 7y ago
      I think it flipped when in the body, so however long the shelf life was, it still wouldn't matter. Incidentally, and AIUI, the body has a tagging system for unwanted proteins. Once tagged, the proteins are removed. Thalidomide tagged the proteins the were specific to embryonic limb formation, and the body duly cleared them, leading to the infamous result. Again AIUI.

skissane 7y ago

Not a biologist or chemist either, but I'll try to give my layperson understanding: basically, many molecules exist in two different versions which are mirror images of each other (enantiomers). Most drugs are actually an equal mixture of both enantiomers (called a racemic mixture), but often only one of the enantiomers has the desired drug effect, and the other doesn't actually do anything. It is possible to create a drug which has only the effective enantiomer; usually, a pure dose of the effective enantiomer will be effective at half the dose as the racemic mixture. Medically, there are some advantages – both forms need to be metabolised by the liver, so being able to use half the dose to get the same effect gives the liver less work to do, which can reduce the risk of drug-induced liver injury. If the racemic mixture is already being widely used, then the risk of the pure effective enantiomer is likely to be low, since it is basically just a more effective form of the already used drug, and the side effect profile should be similar to the existing drug. Chemically, the manufacturing process is more complex, which adds to manufacturing costs; however, the main driver of additional costs is that you can get a new patent for the active enantiomer even after the patent on the racemic mixture is expired. For example, the common SSRI anti-depressant citalopram is the racemic mixture, whereas escitalopram is the S-enantiomer. Similarly, esketamine would be the S-enantiomer of ketamine.