Editing Zolmitriptan

{{Short description|Medication used in treatment of migraines}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 477869605
| IUPAC_name = (''S'')-4-({3-[2-(Dimethylamino)ethyl]-1''H''-indol-5-yl}methyl)-1,3-oxazolidin-2-one
| image = Zolmitriptan.svg
| width = 220
| image2 = Zolmitriptan 3D BS.png
| width2 = 220

<!-- Clinical data -->| tradename = Zomig, others
| Drugs.com = {{drugs.com|monograph|zolmitriptan}}
| MedlinePlus = a601129
| DailyMedID = Zolmitriptan
| pregnancy_AU = B3
| routes_of_administration = [[Oral administration|By mouth]], [[nasal administration|intranasal]]
| class = [[Serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub>]] and [[5-HT1D receptor|5-HT<sub>1D</sub> receptor]] [[agonist]]; [[Antimigraine agent]]; [[Triptan]]

<!-- Legal status -->| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=[[Health Canada]] | date=6 June 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=8 June 2024}}</ref>
| legal_US = Rx-only

<!-- Pharmacokinetic data -->| bioavailability = [[Oral administration|Oral]]: 40%<ref name="DrugBank" />
| protein_bound = 25%<ref name="DrugBank" />
| metabolism = [[Liver]] ([[CYP1A2]]-mediated, to active metabolite; also {{Abbrlink|MAO|monoamine oxidase}})<ref name="DrugBank" />
| metabolites = • ''N''-Desmethylzolmitriptan<ref name="DrugBank" /><br />• Zolmitriptan ''N''-oxide<ref name="DrugBank" /><br />• Indole acetic acid derivative<ref name="DrugBank" />
| elimination_half-life = Zolmitriptan: 3{{nbsp}}hours<ref name="DrugBank">{{cite web | title=Zolmitriptan: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=25 November 1997 | url=https://go.drugbank.com/drugs/DB00315 | access-date=27 October 2024}}</ref><br />''N''-Desmethylzolmitriptan: 3.5{{nbsp}}hours<ref name="DrugBank" />
| excretion = [[Urine]]: ~65%<ref name="DrugBank" /><br />[[Feces]]: ~30%<ref name="DrugBank" />

<!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 139264-17-8
| ATC_prefix = N02
| ATC_suffix = CC03
| ATC_supplemental = 
| PubChem = 60857
| IUPHAR_ligand = 60
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00315
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 54844
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2FS66TH3YW
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00415
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 10124
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1185
| synonyms = BW-311C90; BW311C90; 311C90; BW-311-C-90; ML-004; ML004; [(4''S'')-2-Oxo-1,3-oxazolidin-4-yl]methyl-''N'',''N''-dimethyltryptamine

<!-- Chemical data -->| C = 16
| H = 21
| N = 3
| O = 2
| SMILES = O=C1OC[C@@H](N1)Cc2ccc3c(c2)c(c[nH]3)CCN(C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H21N3O2/c1-19(2)6-5-12-9-17-15-4-3-11(8-14(12)15)7-13-10-21-16(20)18-13/h3-4,8-9,13,17H,5-7,10H2,1-2H3,(H,18,20)/t13-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ULSDMUVEXKOYBU-ZDUSSCGKSA-N
}}
<!-- Definition and medical uses -->
'''Zolmitriptan''', sold under the brand name '''Zomig''' among others, is a [[serotonergic drug|serotonergic]] [[medication]] which is used in the acute treatment of [[migraine]] attacks with or without [[aura (symptom)|aura]] and [[cluster headache]]s.<ref name="Zolmig-Label">{{Cite web| title=Highlights of prescribing information | url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020768s023,021231s014,021450s010lbl.pdf | archive-url=https://web.archive.org/web/20210328172742/https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020768s023,021231s014,021450s010lbl.pdf | archive-date=2021-03-28}}</ref> It is taken [[oral administration|by mouth]] as a [[swallowing|swallowed]] or [[orally disintegrating tablet|disintegrating]] [[tablet (pharmacy)|tablet]] or as a [[nasal spray]].<ref name="Zolmig-Label" />

<!-- Side effects, mechanism of action, and chemistry -->
[[Side effect]]s include tightness in the neck or throat, [[Orofacial pain|jaw pain]], [[dizziness]], [[paresthesia]], [[asthenia]], [[somnolence]], warm/cold sensations, [[nausea]], [[chest pressure]], and [[dry mouth]].<ref name="Zolmig-Label" /> The drug acts as a [[binding selectivity|selective]] [[serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub>]] and [[5-HT1D receptor|5-HT<sub>1D</sub> receptor]] [[agonist]].<ref name="Zolmig-Label" /> [[Chemical structure|Structurally]], it is a [[triptan]] and a [[substituted tryptamine|tryptamine]] [[chemical derivative|derivative]].<ref name="Zolmig-Label" /><ref name="PubChem">{{cite web | title=Zolmitriptan | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/60857 | access-date=27 October 2024}}</ref>

<!-- History, society, and culture -->
It was [[patent]]ed in 1990 and was approved for medical use in 1997.<ref name="Fis2006">{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=531 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA531 |language=en}}</ref><ref name="Zolmig-Label" />

==Medical uses ==
===Migraine===
Zolmitriptan is used for the acute treatment of [[migraine]]s with or without [[aura (symptom)|aura]] in adults.<ref name="Zolmig-Label" /> It is not intended for the [[prophylaxis|prophylactic]] therapy of migraine or for use in the management of [[hemiplegic migraine|hemiplegic]] or [[basilar migraine]].<ref name="Zolmig-Label" />

===Off-label uses===
* Acute treatment of [[cluster headache]]s—Level A recommendation from the American Academy of Neurology<ref name=statspe>{{cite journal | vauthors = Abram JA, Patel P | title = Zolmitriptan | journal = Statpearls| date = 2020 | pmid = 32491581}}[[File:CC-BY icon.svg|50px]] Text was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License].</ref>
* Acute treatment of [[menstrual migraine]]<ref name=statspe/>

===Available forms===
Zolmitriptan is available as a [[swallowing|swallowed]] [[tablet (pharmacy)|tablet]], an [[orally disintegrating tablet]], and as a [[nasal spray]], in doses of 2.5 and 5{{nbsp}}mg. People who get migraines from [[aspartame]] should not use the disintegrating tablet (Zomig ZMT) as it contains aspartame.<ref>{{cite journal | journal = Headache: The Journal of Head and Face Pain | year = 2001 | volume = 41 | issue =9 | pages = 899–901 | doi= 10.1046/j.1526-4610.2001.01164.x | title =Migraine MLT-Down: An Unusual Presentation of Migraine in Patients With Aspartame-Triggered Headaches |vauthors=Newman LC, Lipton RB | doi-broken-date = 9 December 2024 | pmid = 11703479 | type =abstract}}</ref>

A 2014 [[Cochrane review]] has shown that zolmitriptan 5{{nbsp}}mg nasal spray was significantly more effective than the 5{{nbsp}}mg oral tablet.<ref name="BirdDerryMoore2014">{{cite journal |vauthors=Bird S, Derry S, Moore RA |title=Zolmitriptan for acute migraine attacks in adults |journal=Cochrane Database Syst Rev |issue=5 |pages=CD008616 |date=May 2014 |volume=2014 |pmid=24848613 |pmc=6485805 |doi=10.1002/14651858.CD008616.pub2 }}</ref>

==Contraindications==
Zolmitriptan is contraindicated in patients with cerebrovascular or cardiovascular disease because [[serotonin]] [[5-HT1B receptor|5-HT<sub>1B</sub> receptor]]s are present in coronary arteries. Such conditions include, but are not limited to, coronary artery disease, stroke, and peripheral vascular disease.<ref name=statspe/> It is also contraindicated in [[hemiplegic migraine]].<ref name=statspe/>

==Side effects==
[[Side effect]]s include [[neck]]/[[throat]]/[[jaw]] [[pain]]/tightness/pressure, [[dizziness]], [[paresthesia]], [[asthenia]], [[somnolence]], warm/cold sensations, [[nausea]], heaviness sensation, and [[dry mouth]].<ref name="Zolmig-Label" />

As for cardiovascular [[side effect]]s, zolmitriptan can increase systolic blood pressure in the elderly and increase diastolic blood pressure in both the elderly and young people. Additionally, there is the side effect of a [[dose dependence|dose-related]] increase in [[sedation]]. There is a risk for [[headache attributed to a substance or its withdrawal|medication withdrawal headache]] or [[medication overuse headache]].<ref name="statspe" />

Zolmitriptan has a weak [[affinity (pharmacology)|affinity]] for [[serotonin]] [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]]s; these [[receptor (biochemistry)|receptor]]s have been implicated in the development of [[serotonin syndrome]].<ref name="statspe" />

==Interactions==
Following administration of [[cimetidine]], the [[elimination half-life]] and [[area-under-the-curve (pharmacokinetics)|total exposure]] of zolmitriptan and its [[active metabolite]] were approximately doubled.<ref name="statspe" />

==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/>

==Chemistry==
Zolmitriptan is a [[triptan]] and a [[substituted tryptamine]].<ref name="Zolmig-Label" /><ref name="PubChem" /> It is specifically the [[chemical derivative|derivative]] of [[dimethyltryptamine|''N'',''N''-dimethyltryptamine]] (DMT) in which the [[hydrogen]] [[atom]] at position 5 of the [[indole]] [[ring (chemistry)|ring]] has been [[chemical substituent|substituted]] with a [(4''S'')-2-oxo-1,3-oxazolidin-4-yl]methyl [[functional group|group]].<ref name="PubChem" />

The experimental [[partition coefficient|log P]] of zolmitriptan is 1.6 to 1.8.<ref name="PubChem" /> For comparison, the experimental log P of [[sumatriptan]] is 0.93.<ref name="PubChem-Sumatriptan">{{cite web | title=Sumatriptan | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/5358 | access-date=27 October 2024}}</ref> It is much more [[lipophilic]] than sumatriptan.<ref name="Tfelt-HansenDeVriesSaxena2000">{{cite journal | vauthors = Tfelt-Hansen P, De Vries P, Saxena PR | title = Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy | journal = Drugs | volume = 60 | issue = 6 | pages = 1259–1287 | date = December 2000 | pmid = 11152011 | doi = 10.2165/00003495-200060060-00003 | url = }}</ref>

[[Structural analog|Analogue]]s of zolmitriptan include other triptans like sumatriptan, [[naratriptan]], [[rizatriptan]], [[eletriptan]], [[almotriptan]], and [[frovatriptan]].<ref name="Tfelt-HansenDeVriesSaxena2000" />

==Society and culture==
===Brand names===
Zolmitriptan is marketed by [[AstraZeneca]] with the brand names Zomig, Zomigon (Argentina, Canada, and Greece), AscoTop (Germany) and Zomigoro (France).

===Economics===
In 2008, Zomig generated nearly $154 million in sales.<ref>{{cite web|url= http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard//drugtopics/192009/597083/article.pdf |archive-url= https://web.archive.org/web/20090521090922/http://drugtopics.modernmedicine.com:80/drugtopics/data/articlestandard/drugtopics/192009/597083/article.pdf |url-status= dead |archive-date= 2009-05-21 |title=2008 Top 200 generic drugs by retail dollars }} &nbsp;{{small|(332&nbsp;KB)}}. ''Drug Topics'' (May 26, 2009). Retrieved on August 25, 2009.</ref>

AstraZeneca's U.S. patent on Zomig tablets expired on November 14, 2012, and its pediatric exclusivity extension expired on May 14, 2013.<ref>{{Cite web|url=https://www.drugs.com/availability/generic-zomig-zmt.html|title=Generic Zomig-ZMT Availability|website=Drugs.com}}</ref> The patent in certain European countries has already expired too, and generic drug maker [[Actavis]] released a generic version in those countries, starting in March 2012.<ref>{{cite web |url=http://www.actavis.com/en/media+center/newsroom/articles/migraine_zolmitriptan_eu.htm |url-status=dead |archive-url=https://web.archive.org/web/20120323050048/http://www.actavis.com/en/media+center/newsroom/articles/migraine_zolmitriptan_eu.htm |archive-date=2012-03-23 |title=Migraine treatment Zolmitriptan launched by Actavis in Europe}}</ref>

===Legal status===
In [[Russia]], versions of zolmitriptan which are not registered in the National registry of medications may be regarded as narcotic drugs (derivatives of [[N,N-Dimethyltryptamine|dimethyltriptamine]]).<ref name="Order681">{{cite web|url=http://base.garant.ru/12112176/|title=Постановление Правительства РФ от 30 июня 1998 г. N 681 "Об утверждении перечня наркотических средств, психотропных веществ и их прекурсоров, подлежащих контролю в Российской Федерации" (с изменениями и дополнениями)|quote=ДМТ (диметилтриптамин) и его производные, за исключением производных, включенных в качестве самостоятельных позиций в перечень|publisher=[[Гарант (справочно-правовая система)|Гарант]]|access-date=2019-04-29|lang=ru}}</ref>

==Research==
===Obsessive–compulsive disorder===
Zolmitriptan showed no effect on [[obsessive–compulsive disorder]] (OCD) symptoms nor on [[mood (psychology)|mood]] or [[anxiety]] in a [[clinical study]].<ref name="TigerVarnäsOkubo2018">{{cite journal | vauthors = Tiger M, Varnäs K, Okubo Y, Lundberg J | title = The 5-HT1B receptor - a potential target for antidepressant treatment | journal = Psychopharmacology (Berl) | volume = 235 | issue = 5 | pages = 1317–1334 | date = May 2018 | pmid = 29546551 | pmc = 5919989 | doi = 10.1007/s00213-018-4872-1 | url = }}</ref><ref name="BoshuisendenBoer2000">{{cite journal | vauthors = Boshuisen ML, den Boer JA | title = Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder | journal = Psychopharmacology (Berl) | volume = 152 | issue = 1 | pages = 74–79 | date = September 2000 | pmid = 11041318 | doi = 10.1007/s002130000529 | url = }}</ref>

===Social deficits and aggression===
{{See also|Serenic#Examples|Empathogen#Mechanism of action|List of investigational aggression drugs}}

Zolmitriptan, in a [[modified-release dosage|modified-release]] [[drug formulation|formulation]] with code name ''ML-004'' (or ''ML004''), is under development by MapLight Therapeutics for the treatment of [[pervasive developmental disorder]]s (e.g., [[autism]]), [[psychomotor agitation|agitation]], and [[aggression]].<ref name="AdisInsight-ML-004">{{cite web | title=ML 004 | website=AdisInsight | date=8 June 2023 | url=https://adisinsight.springer.com/drugs/800061291 | access-date=27 October 2024}}</ref><ref name="Synapse2024">{{cite web | title=Delving into the Latest Updates on ML-004 with Synapse | website=Synapse | date=28 September 2024 | url=https://synapse.patsnap.com/drug/64e037a51d55415f8f4919a04aef3082 | access-date=27 October 2024}}</ref><ref name="TheTransmitter2023">{{cite web | last=Hess | first=Peter | title=Going on Trial: Serotonin drug; psilocybin phase 2; placebo response data | website=The Transmitter: Neuroscience News and Perspectives | date=28 April 2023 | url=https://www.thetransmitter.org/spectrum/going-on-trial-serotonin-drug-psilocybin-phase-2-placebo-response-data/ | access-date=27 October 2024}}</ref><ref name="WangClarkHanratty2024">{{cite journal | vauthors = Wang L, Clark EA, Hanratty L, Koblan KS, Foley A, Dedic N, Bristow LJ | title = TAAR1 and 5-HT1B receptor agonists attenuate autism-like irritability and aggression in rats prenatally exposed to valproic acid | journal = Pharmacol Biochem Behav | volume = 245 | issue = | pages = 173862 | date = August 2024 | pmid = 39197535 | doi = 10.1016/j.pbb.2024.173862 | url = | quote = Interest in 5-HT1B as a target for ASD is further evidenced by the ongoing Phase 2 clinical trial of ML-004, a modified release form of the 5-HT1B/1D agonist zolmitriptan, which is being evaluated for the treatment of social communication deficits in adolescent and adult subjects with ASD (NCT05081245).}}</ref><ref name="Cortica">{{cite web | title=Maplight Autism Study | website=Cortica | url=https://www.corticacare.com/research/maplight | access-date=27 October 2024 | quote=Purpose: The purpose of this study is to find out whether ML-004, an extended-release version of zolmitriptan, can support with sociability and emotional regulation in adults with ASD.}}</ref><ref name="PharmTech2024">{{cite web | url=https://www.pharmaceutical-technology.com/data-insights/zolmitriptan-maplight-therapeutics-autism-spectrum-disorder-asd-likelihood-of-approval/ | archive-url=https://web.archive.org/web/20240522133617/https://www.pharmaceutical-technology.com/data-insights/zolmitriptan-maplight-therapeutics-autism-spectrum-disorder-asd-likelihood-of-approval/ | archive-date=22 May 2024 | title=Zolmitriptan by MapLight therapeutics for Autism Spectrum Disorder (ASD): Likelihood of Approval }}</ref> The drug has been found to reduce aggression in rodents<ref name="Rasia-FilhoGiovenardide Almeida2008">{{cite journal | vauthors = Rasia-Filho AA, Giovenardi M, de Almeida RM | title = Drugs and aggression | journal = Recent Pat CNS Drug Discov | volume = 3 | issue = 1 | pages = 40–49 | date = January 2008 | pmid = 18221240 | doi = 10.2174/157488908783421456 | url = | quote = In addition, the 5-HT1B receptors are of potential importance as target for treatment of different disorders such as depression, schizophrenia, Parkinson’s disease, and impulsive disorders [133]. Drugs acting as agonists at 5- HT1B receptors, when administered systemically, potently and efficaciously inhibit several types of aggressive behavior in mice [17,135; and for review see 63]. Systemically administered 5-HT1B receptor agonists such as CP-94,253, ampirtoline and zolmitriptan exert anti-aggressive effects in mice with moderate or high levels of aggression, without impairing non-aggressive activities [17, 23, 129,135]. Further support for the significant role of this receptor subtype derives from the finding of increased aggression in mutant 129Sv mice lacking the 5-HT1B receptor gene [136, and see 137].}}</ref><ref name="deBoerKoolhaas2005">{{cite journal | vauthors = de Boer SF, Koolhaas JM | title = 5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis | journal = Eur J Pharmacol | volume = 526 | issue = 1-3 | pages = 125–139 | date = December 2005 | pmid = 16310183 | doi = 10.1016/j.ejphar.2005.09.065 | url = | quote = Using such an ethopharmacological approach in either rats or mice, it has recently been claimed that only certain specific 5-HT1A receptor agonists (i.e., alnespirone and S-15535; de Boer et al., 1999, 2000), a mixed 5-HT1A/1B receptor agonist (i.e., eltoprazine; Olivier et al., 1995) and several specific 5-HT1B receptor agonists (i.e., CGS12066b, CP-94,253, anpirtoline, zolmitriptan, sumatriptan; Bell and Hobson, 1994; Fish et al., 1999; De Almeida et al., 2001; Miczek et al., 2004) exert behavioral specific anti-aggressive effects. In particular, it was claimed that agonists acting on the 5-HT1B receptors have more selective anti-aggressive effects in mice than those acting on 5-HT1A receptors (Miczek et al., 2004; Olivier, 2004).}}</ref><ref name="deAlmeidaNikulinaFaccidomo2001">{{cite journal | vauthors = de Almeida RM, Nikulina EM, Faccidomo S, Fish EW, Miczek KA | title = Zolmitriptan--a 5-HT1B/D agonist, alcohol, and aggression in mice | journal = Psychopharmacology (Berl) | volume = 157 | issue = 2 | pages = 131–141 | date = September 2001 | pmid = 11594437 | doi = 10.1007/s002130100778 | url = }}</ref> and has also been reported to decrease aggression in humans.<ref name="TricklebankRobbinsSimmons2021">{{cite journal | vauthors = Tricklebank MD, Robbins TW, Simmons C, Wong EH | title = Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology | journal = Psychopharmacology (Berl) | volume = 238 | issue = 6 | pages = 1417–1436 | date = June 2021 | pmid = 33694032 | pmc = 7945970 | doi = 10.1007/s00213-021-05787-x | url = | quote = A high proportion of violent acts are committed under the influence of alcohol. Aggressive behaviour can also be primed in the mouse by exposure to alcohol (De Almeida et al. 2001). In findings that are consistent with our knowledge of the relationship between serotonin and aggression (Pihl and Lemarquand 1998), this impact of alcohol can be ameliorated by treatment with the 5-HT1B/1D receptor agonist zolmitriptan, an approved anti-migraine drug. However, these findings have seemingly been overlooked despite the consistency of rodent and human data (Gowin et al. 2010).}}</ref><ref name="GowinSwannMoeller2010">{{cite journal | vauthors = Gowin JL, Swann AC, Moeller FG, Lane SD | title = Zolmitriptan and human aggression: interaction with alcohol | journal = Psychopharmacology (Berl) | volume = 210 | issue = 4 | pages = 521–531 | date = July 2010 | pmid = 20407761 | pmc = 9150756 | doi = 10.1007/s00213-010-1851-6 | url = }}</ref> As of June 2023, zolmitriptan is in [[Phases of clinical research#Phase II|phase 2]] [[clinical trial]]s for pervasive developmental disorders, [[Phases of clinical research#Phase I|phase 1]] clinical trials for agitation, and is in the [[preclinical research|preclinical stage of development]] for aggression.<ref name="AdisInsight-ML-004" /><ref name="Synapse2024" /><ref name="TheTransmitter2023" />

==References==
{{Reflist}}

==Further reading==
* {{cite journal | journal = Drugs Today | year = 1998 | volume = 34 | issue = 12 | pages = 1027–1033 | doi = 10.1358/dot.1998.34.12.487488 | title = Zolmitriptan clinical studies | vauthors = MacGregor EA | pmid = 14743270}}

==External links==
* {{cite web | title=Zolmitriptan Nasal Spray | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a605046.html }}

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