KarXT Demonstrated Statistically Significant and Clinically Meaningful Improvement in Total PANSS Score at All Time Points Over Five Weeks and was Well-Tolerated Compared to Placebo
Improvement in Total PANSS Score at Five Weeks was 11.6 Points Compared to Placebo (p<0.0001)
No Evidence of Somnolence, Extrapyramidal Side Effects or Weight Gain Relative to Placebo
Data Support Advancing KarXT to Phase 3 and Continued Development in Other CNS Disorders
Yay we have hope
what about negative and cognitive symptoms.!!
What about sexual dysfunction, does it affect that?
Roughly, how long till this gets approved?
Thanks
5 To 7 years…!!
That’s far too long.
2023 or somewhere near should be release if it pass’s phase 3, there was no mention of any sexual dysfunction so hopefully it dosnt effect it.
Does this work on dopamine? From my reading, it affects the muscaric receptors, which I presume means it doesn’t affect dopamine. Pretty big if true.
Ahh, just read that it is still anti-dopaminergic. Oh well, looks like we will still be stuck with negative symptoms.
Its in phase 1 for neg and cog, So it may help with those symptoms.
It might do, but the fact it is still acting on dopamine makes me doubt this. We need something revolutionary, and I don’t think this is it. CBD may be the best hope.
Cannabidiol is a partial D2 agonist, although that’s not its only apparent mechanism of action.
It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects.
Yes, I’ve read that, but I’ve also read other papers saying they still don’t know the mechanism of action. I guess I’m hoping more than anything.
Here’s another recent one from Sagnik Bhattacharyya (Kings College London guy) that rehashes research up until now, but still postulates a potential non-dopaminergic method of action. Like I say, I live in hope.
It is hard to read these studies without a pharmaceutical background, as it is impossible to distinguish the good studies from the bad ones.
https://journals.sagepub.com/doi/full/10.1177/2045125319881916
Well, we don’t know which of its various actions is potentially useful or if several of them in combination are. It does seem to interact with D2, possibly more directly than KarXt.
NaBen and Evenamide as far as I know, do not. However, it’s always possible that some part of their functionality is because of downstream modulation of dopamine.
It’s not quite so simple as dopamine blockers causing negative symptoms since unmedicated people also have them, but obviously the current ones have serious side effects that hopefully these new ones won’t. If their action is indirect, that may help with a lot of the side effects. If you overproduce dopamine in the wrong area of the brain (and underproduce it in others) something that works upstream to prevent the overproduction vs just blocking it might be better.
Maybe in the next 20 - 30 years.
Yeah something big will happen in the next 20-30 years, maybe something like this:
But it’s not near…
AUT00206 is also a non-dopaminergic medication - at least not directly, but it may indirectly help normalize dopamine function. It’s just completed phase 1b so they don’t completely understand its pharmacodynamics yet. It is a potassium channel modulator.
Specifically, parvalbumin+ cells are now also being explored as a novel approach to repairing DLPFC neural circuitry and improving the cognitive symptom domain in schizophrenia (Clinicaltrials.gov Identifier: NCT03164876). Parvalbumin+ cells innervate multiple pyramidal cells and contain lower mRNA for parvalbumin and GAD67 in those with schizophrenia (124) and reduced expression of the potassium channel KCNS3 gene which encodes the Kv9.3 potassium channel α subunit and is essential for control over its fast-spiking abilities (197). Inhibitory parvalbumin+ interneurons contribute to the cognitive deficits in schizophrenia (115) and in unmedicated patients with the illness.
I’m not getting too excited about this one yet since it is early phase but it is very intriguing and novel. Autifony and BI propose it for cognitive and negative symptoms.