Editing Zolmitriptan (section)

==Pharmacology==
===Mechanism of action===
Zolmitriptan is a [[binding selectivity|selective]] [[serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub>]] and [[5-HT1D receptor|5-HT<sub>1D</sub> receptor]] [[agonist]] with weak [[affinity (pharmacology)|affinity]] for the serotonin [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]].<ref name="Tfelt-HansenDeVriesSaxena2000" /> It also has affinity for other [[serotonin receptor]]s, including the serotonin [[5-HT1E receptor|5-HT<sub>1E</sub>]], [[5-HT1F receptor|5-HT<sub>1F</sub>]], [[5-HT2B receptor|5-HT<sub>2B</sub>]], [[5-HT5A receptor|5-HT<sub>5A</sub>]], and [[5-HT7 receptor|5-HT<sub>7</sub> receptor]]s.<ref name="Tfelt-HansenDeVriesSaxena2000" /> Conversely, its affinities for the serotonin [[5-HT2A receptor|5-HT<sub>2A</sub>]], [[5-HT2C receptor|5-HT<sub>2C</sub>]], [[5-HT3 receptor|5-HT<sub>3</sub>]], [[5-HT4 receptor|5-HT<sub>4</sub>]], and [[5-HT6 receptor|5-HT<sub>6</sub> receptor]]s are negligible or undetectable.<ref name="Tfelt-HansenDeVriesSaxena2000" />

Its action on serotonin 5-HT<sub>1B</sub> and 5-HT<sub>1D</sub> receptors causes [[vasoconstriction]] in [[intracranial]] [[blood vessel]]s; as well it can inhibit the release of [[pro-inflammatory]] [[neuropeptide]]s from [[trigeminal]] [[perivascular]] [[nerve ending]]s. It crosses the [[blood–brain barrier]] as evidenced by the presence of [[radiolabel]]ed zolmitriptan within the cells of the trigeminal nucleus caudalis and nucleus tractus solitarii.<ref name=statspe/>

===Pharmacokinetics===
Zolmitriptan has a rapid onset of action and has been detected in the brain as early as within 5 minutes of intranasal administration. On average, zolmitriptan has an oral bioavailability of 40%, a mean volume of distribution of 8.3 L/kg after oral administration, and 2.4L/kg after intravenous administration.<ref name=statspe/> According to a study of healthy volunteers, food intake seems to have no significant effect on the effectiveness of zolmitriptan in both men and women.<ref>{{cite journal | vauthors = Seaber EJ, Peck RW, Smith DA, Allanson J, Hefting NR, van Lier JJ, Sollie FA, Wemer J, Jonkman JH | display-authors = 6 | title = The absolute bioavailability and effect of food on the pharmacokinetics of zolmitriptan in healthy volunteers | journal = British Journal of Clinical Pharmacology | volume = 46 | issue = 5 | pages = 433–439 | date = November 1998 | pmid = 9833595 | pmc = 1873688 | doi = 10.1046/j.1365-2125.1998.00809.x | type = abstract }}</ref>

Zolmitriptan is a more [[lipophilic]] [[chemical compound|compound]] with greater [[central nervous system|central]] [[drug permeability|permeability]] than certain other [[triptan]]s like [[sumatriptan]].<ref name="Martin1997">{{cite journal | vauthors = Martin GR | title = Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine | journal = Cephalalgia | volume = 17 Suppl 18 | issue = | pages = 4–14 | date = October 1997 | pmid = 9399012 | doi = 10.1177/0333102497017S1802 | url = }}</ref><ref name="LionettoCasollaMastropietri2012">{{cite journal | vauthors = Lionetto L, Casolla B, Mastropietri F, D'Alonzo L, Negro A, Simmaco M, Martelletti P | title = Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines | journal = Expert Opin Drug Metab Toxicol | volume = 8 | issue = 8 | pages = 1043–1050 | date = August 2012 | pmid = 22762358 | doi = 10.1517/17425255.2012.701618 | url = }}</ref> It has been found to cross the [[blood–brain barrier]] and enter the [[central nervous system]] both in animals and humans.<ref name="DeenChristensenHougaard2017">{{cite journal | vauthors = Deen M, Christensen CE, Hougaard A, Hansen HD, Knudsen GM, Ashina M | title = Serotonergic mechanisms in the migraine brain - a systematic review | journal = Cephalalgia | volume = 37 | issue = 3 | pages = 251–264 | date = March 2017 | pmid = 27013238 | doi = 10.1177/0333102416640501 | url = | quote = The central mechanisms of triptans are a subject of intense debate and have been investigated in several studies. Brain PET studies reported that zolmitriptan crosses the BBB and binds to central 5-HT1B receptors with relatively low occupancy (77,78). It is still unknown whether sumatriptan has a central effect.}}</ref> In a clinical [[pharmacokinetic]] study, brain concentrations were about 20% of plasma concentrations.<ref name="WallKågedalBergström2005" /> However, in another clinical study, the drug achieved relatively low [[receptor occupancy|occupancy]] of central [[serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub> receptor]]s (4–5%) as measured by [[positron emission tomography]] (PET) [[medical imaging|imaging]].<ref name="DeenChristensenHougaard2017" /><ref name="VarnäsJučaiteMcCarthy2013">{{cite journal | vauthors = Varnäs K, Jučaite A, McCarthy DJ, Stenkrona P, Nord M, Halldin C, Farde L, Kanes S | title = A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers | journal = Cephalalgia | volume = 33 | issue = 10 | pages = 853–860 | date = July 2013 | pmid = 23430984 | doi = 10.1177/0333102413476372 | url = }}</ref><ref name="WallKågedalBergström2005">{{cite journal | vauthors = Wall A, Kågedal M, Bergström M, Jacobsson E, Nilsson D, Antoni G, Frändberg P, Gustavsson SA, Långström B, Yates R | title = Distribution of zolmitriptan into the CNS in healthy volunteers: a positron emission tomography study | journal = Drugs in R&D | volume = 6 | issue = 3 | pages = 139–147 | date = 2005 | pmid = 15869317 | doi = 10.2165/00126839-200506030-00002 | url = }}</ref>

Zolmitriptan is [[drug metabolism|metabolized]] into three major [[metabolite]]s by the human [[liver|hepatic]] [[cytochrome P450]] [[enzyme]]s—primarily [[CYP1A2]]. Two-thirds of the parent compound breaks down into the [[active metabolite]] ''N''-desmethylzolmitriptan (183C91), while the remaining one-third separates into the other two inactive [[metabolite]]s: zolmitriptan ''N''-oxide and an [[indole-3-acetic acid|indole acetic acid]] [[chemical derivative|derivative]]. It has an [[elimination half-life]] of about 3{{nbsp}}hours before it undergoes [[kidney|renal]] [[elimination (pharmacology)|elimination]]; its [[clearance (pharmacology)|clearance]] is greater than the [[glomerular filtration rate]] suggesting that there is some renal tubular secretion of the compound.<ref name=statspe/>