5-hydroxytryptamine receptor 2C (5-HT2C) and adrenergic receptors (5-HT2C/Adrenoceptors)

The 5-hydroxytryptamine receptor 2C (5-HT2C) and adrenergic receptors are distinct classes of G protein-coupled receptors (GPCRs) that are frequently co-targeted by psychotropic medications. The 5-HT2C receptor is primarily expressed in the central nervous system, where it modulates mood, anxiety, and satiety; its activation is a key mechanism for appetite suppression, while its antagonism is associated with the efficacy of certain antidepressants and antipsychotics (UniProt P28335; StatPearls NBK545168). Adrenergic receptors, divided into alpha and beta subtypes, mediate the effects of norepinephrine and epinephrine across the central and peripheral nervous systems, influencing cardiovascular tone, metabolic rate, and alertness (StatPearls NBK539830). Drugs that interact with both 5-HT2C and adrenergic subtypes, such as mirtazapine or clozapine, leverage these interactions to treat complex conditions like major depressive disorder and treatment-resistant schizophrenia (IUPHAR/BPS Guide to Pharmacology). However, off-target effects on these receptors can lead to side effects such as orthostatic hypotension via alpha-1 blockade or metabolic changes (PubMed PMID: 10446768). Understanding the polypharmacology of these receptors is essential for managing the therapeutic window of many CNS-active drugs.

Other names

5-HT2CHTR2CSerotonin 2C receptorAdrenoceptorsAdrenergic receptorsAlpha-adrenergic receptorsBeta-adrenergic receptors

Agonism of 5-HT2C receptors for weight management; antagonism of 5-HT2C and alpha-2 adrenergic receptors for antidepressant effects; antagonism of alpha-1 adrenergic receptors for antihypertensive effects.