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dc.contributor.authorPalacios, José M.es_ES
dc.contributor.authorPazos Carro, Ángel es_ES
dc.contributor.authorHoyer, Danieles_ES
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.date.accessioned2018-04-03T08:37:32Z
dc.date.available2018-05-01T02:45:15Z
dc.date.issued2017es_ES
dc.identifier.issn0033-3158es_ES
dc.identifier.issn1432-2072es_ES
dc.identifier.urihttp://hdl.handle.net/10902/13422
dc.description.abstractThis paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain.es_ES
dc.format.extent24 p.es_ES
dc.language.isoenges_ES
dc.publisherSpringeres_ES
dc.rights©Springer. The final publication is available at Springer via http://dx.doi.org/10.1007/s00213-017-4545-5es_ES
dc.sourcePsychopharmacology (Berl). 2017 May;234(9-10):1395-1418es_ES
dc.titleA short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatmentes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsopenAccesses_ES
dc.identifier.DOI10.1007/s00213-017-4545-5es_ES
dc.type.versionacceptedVersiones_ES


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