A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This 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

Correlation of formative assessments as the means of predicting summative performance in paramedic students

Batt, AM ORCiD: 0000-0001-6473-5397Leggio WJ, Batt AM, Berry JC, Fentress T, Vosper ML, Walsh K, et al. Correlation of formative assessments as the means of predicting summative performance in paramedic students. The Internet Journal of Allied Health Sciences and Practice. 2017 Oct 03;15(4), Article 2. Correlation of formative assessments as the means of predicting summative performance in paramedic students Background: Paramedic programs use formative assessments to determine cognitive competency. Understanding the number of failed formative units as a probability of passing the summative exam will allow programs to set additional benchmarks. The purpose of this study was to determine whether failure in formative exams determines success on a summative exam

Correlation of formative assessments as the means of predicting summative performance in paramedic students

Leggio WJ, Batt AM, Berry JC, Fentress T, Vosper ML, Walsh K, et al. Correlation of formative assessments as the means of predicting summative performance in paramedic students. The Internet Journal of Allied Health Sciences and Practice. 2017 Oct 03;15(4), Article 2. Correlation of formative assessments as the means of predicting summative performance in paramedic students Background: Paramedic programs use formative assessments to determine cognitive competency. Understanding the number of failed formative units as a probability of passing the summative exam will allow programs to set additional benchmarks. The purpose of this study was to determine whether failure in formative exams determines success on a summative exam