5-hydroxytryptamine receptor 1A (5-HT1A), 5-hydroxytryptamine receptor 2C (5-HT2C), and 5-hydroxytryptamine receptor 1D (5-HT1D) (5-HT1A/2C/1D)

The 5-hydroxytryptamine receptor 1A (5-HT1A), 2C (5-HT2C, formerly 1C), and 1D (5-HT1D) are distinct subtypes of the serotonin receptor family, all belonging to the G protein-coupled receptor (GPCR) superfamily [1, 2, 3]. 5-HT1A is a Gi/o-coupled receptor that acts as a major inhibitory autoreceptor in the raphe nuclei and a postsynaptic receptor in the limbic system, making it a key target for treating anxiety and depression [1, 5]. The 5-HT1C receptor was reclassified as 5-HT2C due to its coupling with Gq/11 proteins and its structural similarity to the 5-HT2 family; it plays a vital role in regulating appetite, mood, and cerebrospinal fluid production [2, 6]. 5-HT1D is a Gi/o-coupled receptor located on cranial blood vessels and trigeminal nerve endings, where its activation mediates vasoconstriction and inhibits the release of pro-inflammatory neuropeptides, serving as a primary target for antimigraine triptans [3, 7]. These receptors are collectively involved in a wide range of physiological and pathological processes, and their pharmacological modulation is central to the treatment of psychiatric, neurological, and metabolic disorders [4]. However, because this grouping combines receptors with different signaling mechanisms and includes an obsolete name, it is considered a non-standard target classification in modern drug development [2, 4].

Other names

5-HT1A5-HT1C5-HT1D5-HT2CHTR1AHTR1CHTR1DHTR2CSerotonin 1A receptorSerotonin 1C receptorSerotonin 1D receptor5-hydroxytryptamine receptor 1A5-hydroxytryptamine receptor 2C5-hydroxytryptamine receptor 1D

Drugs targeting these receptors act as agonists, partial agonists, or antagonists to modulate intracellular signaling via Gi/o (for 1A and 1D) or Gq/11 (for 2C) proteins, thereby influencing neurotransmitter release, neuronal firing, and vascular tone [1, 2, 3, 4].