otherwise. Combining triptans with ergot alkaloids is contraindicated because of the danger of coronary spasms. In a study from Harvard Medical School and the University of Florida College of Medicine involving 47,968 patients and published on 26 February 2018, concomitant use of a selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor for depression with a triptan for migraine did not demonstrate an increased risk of the serotonin syndrome. Pharmacokinetic interactions (for example, mediated by CYP liver enzymes or transporter proteins) are different for the individual substances; for most triptans, they are mild to absent. Eletriptan blood plasma levels are increased by strong inhibitors of CYP3A4, and frovatriptan levels by CYP1A2 inhibitors such as fluvoxamine. Pharmacology Mechanism of action Their action is attributed to their agonist effects on serotonin 5-HT1B and 5-HT1D receptors in blood vessels (causing their constriction) and nerve endings in the brain, and subsequent inhibition of pro-inflammatory neuropeptide release, including CGRP and substance P. Triptans are selective agents for 5-HT1B and 5-HT1D and have low or even no affinity for other types of 5-HT receptors. 5-HT receptors are classified into seven different families named 5-HT1 to 5-HT7. All receptors are G protein coupled receptors with seven transmembrane domains with the one exception of 5-HT3 receptor which is a ligand gated ion channel. There is a high homology in the amino acid sequence within each family. Each family couples to the same second messenger systems. Subtypes of 5-HT1 are the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F receptors. All 5-HT1D receptors are coupled to inhibition of adenylate cyclase. 5-HT1B and 5-HT1D receptors have been difficult to distinguish on a pharmacological basis. After cloning two distinct genes for 5-HT1B and 5-HT1D receptors, a better insight into distribution and expression in different tissues was gained, except in brain tissue where they are overlapping in several areas. Most mammalian species, including humans, have 5-HT1D binding sites widely distributed throughout the central nervous system. 5-HT1D receptors are found in all areas of the brain but they differ in quantity at each area. An important initiator of head pain is suggested to be the activation of trigeminovascular afferent nerves which upon activation releases neuropeptides such as CGRP, substance P and neurokinin A. Also they are thought to promote neurogenic inflammatory response important for sensitization of sensory afferents, and also transmission and generation of head pain centrally. 5-HT1D has been found responsible for inhibition of