5-HT2A/5-HT2C

Class

inverse agonist/antagonist (pimavanserin-class)

5-HT2A and 5-HT2C are subtypes of the serotonin (5-hydroxytryptamine) receptor family that couple to Gq proteins, triggering intracellular signaling that increases neuronal excitability in cortical and limbic circuits. Unlike simple antagonists, which only block an agonist from activating a receptor, inverse agonists also suppress the receptor's baseline (constitutive) signaling, producing a more complete dampening of downstream activity. Modulating 5-HT2A and 5-HT2C is of interest because these receptors participate in circuits governing perception, mood, and behavior, and their overactivity has been linked to psychotic symptoms such as hallucinations and delusions. A key rationale for this drug class is that psychosis can be addressed without blocking dopamine D2 receptors, the traditional antipsychotic target, whose blockade often causes movement-related side effects, especially problematic in patients whose disease already involves dopamine system dysfunction, such as Parkinson's disease. By acting through a serotonergic rather than dopaminergic route, 5-HT2A/5-HT2C inverse agonists offer an alternative strategy for treating psychosis broadly, including presentations associated with neurodegenerative conditions, while aiming to spare motor and endocrine pathways that dopamine-blocking agents typically affect.