Reply from ChatGPT
KarXT (via xanomeline) has a more specific action on the limbic system due to the activation of M4 muscarinic receptors. This may modulate dopamine release primarily in this area, which is expected to have a positive effect on schizophrenia symptoms with a more favorable side effect profile.
D2 antagonists: These medications block dopamine D2 receptors in multiple areas of the brain, including the mesolimbic system, the nigrostriatal pathway, the mesocortical pathway, and the tuberoinfundibular pathway. This can lead to a reduction in the positive symptoms of schizophrenia, but can also cause side effects due to the wide range of brain areas affected.
Therefore, while KarXT is expected to have a more targeted and specific effect on dopamine modulation in the limbic system, D2 antagonists have a more widespread impact throughout the brain.
Conclusion: KarXT not only does not block dopamine, but it indirectly reduces it in the mesolimbic area.
On the other hand, current antipsychotics adhere to D2 receptors in a lot of brain areas, which generates a lot of negative symptoms.