Schizophrenia.com

How do you think Xanomeline would affect negative symptoms?

It exhibits dopamine antagonism and antipsychotic-like effects despite its lack of affinity for any dopamine receptors and it seems to inhibit dopamine cell firing

Wouldn’t it also not help with negative symptoms because its inhibiting dopamine cell firing? Isn’t it indirectly affecting dopamine in another way?

It may not really help with negative symptoms after all

@Aziz

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Maybe but it may have less metabolic side effects as it doesnt act on dopamine receptors directly.

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I am not sure how muscarinic receptors affect dopamine. KarXT acts on M1 and M4 muscarinic receptors as an agonist. I found this:

“In this study, we showed that dopaminergic neurotransmission is highly dependent on M4 cholinergic muscarinic receptor function”

“We propose that M4 receptor agonists could represent an innovative strategy for the treatment of pathologies associated with hyperdopaminergia.”

https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.04-1575fje

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“We report that M1 deficiency leads to elevated dopaminergic transmission in the striatum”

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