Comment by soulofmischief | Hacker News Reader

Comment by soulofmischief | Hacker News Reader

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> 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.

So a double strength dose of the racemic mixture has a much milder effect than a single strength dose of the strong enantiomer?

> 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.

You do realise we can prescribe whatever dose we like, right? Some drugs I prescribe in grams, some in milligrams and some in micrograms. The strength of a drug is somewhat irrelevant. I'm not going to prescribe a new and expensive drug just because the dose is 150mg when it's well-established, cheap cousin is available that happens to need a dose of 300mg.

It certainly is the context, and I believe it's what OP asked. If it wasn't, it should be, because it's the only question that really matters to me as the prescriber.

If what you're saying about the different pharmacodynamics is true (and this is actually what I'm talking about. I only mentioned milder effect because that seemed to be the difference in pharmacodynamics you were getting at), then this is an important difference. It would still have to somehow be quite different to the effect of the racemic version at any arbitrary dose to be preferentially prescribed.

> You do realise we can prescribe whatever dose we like, right? Some drugs I prescribe in grams, some in milligrams and some in micrograms. The strength of a drug is somewhat irrelevant. I'm not going to prescribe a new and expensive drug just because the dose is 150mg when it's well-established, cheap cousin is available that happens to need a dose of 300mg.

I've no wish to argue here, but I am confused about how this has anything to do with it. No one brought up the idea that the doses would be different. We're talking equivalent doses of either an enantiopure or racemic substance.

> It would still have to somehow be quite different to the effect of the racemic version at any arbitrary dose to be preferentially prescribed.

Like I said, we don't know this about ketamine, thus the trials. But we do know this about amphetamine. You would simply have to experience each enantiomer and the racemic mixture in order to understand what I am saying here. The effects are markedly different. My analogy was coffee vs meth.

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