Dopamine, the antipsychotic molecule: A perspective on mechanisms underlying antipsychotic response variability.
Level 5 - mechanism / opinion, no new human data
Mechanism-based reasoning and theoretical model with no new empirical data
PubMed 28970021 · doi:10.1016/j.neubiorev.2017.09.027
What was done
The authors synthesized pharmacological and clinical literature to propose a theoretical hypothesis explaining antipsychotic response variability and paradoxical clinical deterioration seen with persistent dopamine D2 receptor blockade.
What was found
The abstract reports no primary data or numerical findings. The authors propose that effective antipsychotic doses spare a presynaptic D2 autoreceptor reserve while occupying postsynaptic D2 receptors, allowing endogenous dopamine to stimulate autoreceptors and decrease dopamine synthesis and release as an indirect antipsychotic mechanism.
Why it matters
This framework offers a theoretical rationale for why low-affinity D2 antipsychotics can be clinically effective and why individual therapeutic responses vary.
Limits
This is a narrative theoretical perspective containing no new experimental or human data. The presynaptic D2 autoreceptor reserve model remains an unvalidated hypothesis.
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