5-Hydroxytryptamine receptor 3A (5-HT3A, HTR3A) belongs to the superfamily of ligand-gated ion channels. Serotonin receptors, other than the 5-HT3 subtype, belong to the superfamily of G-protein coupled receptors.

The 5-HT3 receptor is formed by five subunits arranged around a pore forming unit. Receptors could be either monomeric, such as 5-HT3A or heteromeric entities like 5-HT3A/B. Indeed, the type of channel formed displays different pharmacological and electrophysiological characteristics^1,2. To date, five 5-HT3 subunits have been identified and labeled 5-HT3A-E, which show variability in the N-terminus and in the transmembrane region². 5-HT3A and 5-HT3B are the best characterized among the different types.

In general, 5-HT3 receptors are located in the peripheral and central nervous system, in lymphocytes and intestinal enterochromaffine cells². In presynaptic neurons, activation of these receptors leads to an increase in intracellular Ca²⁺ (by both influx and mobilization of intracellular stores), and modulates the release of a number of neurotransmitters and neuropeptides². At the postsynaptic level, activation leads to membrane depolarization^2,3. The 5-HT3A subunit is expressed in GABAergic and enkephalinergic neurons in the spinal dorsal horn thereby marking its possible antinociceptive effect⁴.

5-HT3 receptors have become important targets for which to develop treatments for irritable bowel syndrome (IBS), side effects resulting from chemotherapeutic treatment, schizophrenia and bipolar disorder^1,2.