Hm, could you elaborate on that please? Do you mean the separate as in stereoisomer-wise? Or do you mean that ketamin has multiple effects on the brain or central nervous system, and one is the antidepressant effect and the other is the tripping balls effect? (And obviously pharma would like to find out what's going on exactly in the first case or ... how to block the second case while still having the first effect happen?)
* the stereo-isomers have differing effects: s-ketamine being more inebriating and less anti-depressant, while r-ketamine is less inebriating and has a stronger anti-depressant effect.
* The inebriant effect can be modulated without altering the anti-depressant effect, at least in lab rats. Cannabis is one drug that does this.
* The pharmaceutical company that ran the clinical trials for esketamine likely did so because it is actually the least effective anti-depressant of the two entanomers, and less effective than regular ketamine. By trialing and patenting the less effective one first, they can then patent the more effective one later, and make money longer, by dragging their feet. Esketamine is currently a few hundred dollars a dose (every three days). My ketamine is $70 for ~6 week supply. Capitalism is wonderful.
* fwiw, ketamine triggers other pathways in the brain, including ones that are involved in attention deficit and wakefulness. It has the same effect as amantadine - an ADHD medication. I can't take it after 10 am or so, if I am going to get a decent night's sleep.
Off-label use is great, doctors love it, but ... trials don't show much.
" [...] esketamine’s results are at least as bad as any SSRI’s. If you look at Table 9 in the FDA report, ketamine did notably worse than most of the other antidepressants the FDA has approved recently – including vortioxetine, an SSRI-like medication."
> Another possibility is that everyone made a huge mistake in using left-handed ketamine, and it’s right-handed ketamine that holds the magic. Most previous research was done on a racemic mixture (an equal mix of left-handed and right-handed molecules), and at least one study suggests it was the right-handed ketamine that was driving the results. Pharma decided to pursue left-handed ketamine because it was known to have a stronger effect on NMDA receptors, but – surprise! – ketamine probably doesn’t work through NMDA after all.
I think pharma pursued left-handed ketamine because they could patent it and charge a king's ransom for it, whereas your dog's vet has a bottle of right-handed ketamine for $5.
