Chemistry:Zolmitriptan

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Zolmitriptan, sold under the brand name Zomig among others, is a serotonergic medication which is used in the acute treatment of migraine attacks with or without aura and cluster headaches.[1] It is taken by mouth as a swallowed or disintegrating tablet or as a nasal spray.[1]

Side effects include tightness in the neck or throat, jaw pain, dizziness, paresthesia, asthenia, somnolence, warm/cold sensations, nausea, chest pressure, and dry mouth.[1] The drug acts as a selective serotonin 5-HT1B and 5-HT1D receptor agonist.[1] Structurally, it is a triptan and a tryptamine derivative.[1][2]

It was patented in 1990 and was approved for medical use in 1997.[3][1]

Medical uses

Migraine

Zolmitriptan is used for the acute treatment of migraines with or without aura in adults.[1] It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine.[1]

Off-label uses

  • Acute treatment of cluster headaches—Level A recommendation from the American Academy of Neurology[4]
  • Acute treatment of menstrual migraine[4]

Available forms

Zolmitriptan is available as a swallowed tablet, an orally disintegrating tablet, and as a nasal spray, in doses of 2.5 and 5 mg. People who get migraines from aspartame should not use the disintegrating tablet (Zomig ZMT) as it contains aspartame.[5]

A 2014 Cochrane review has shown that zolmitriptan 5 mg nasal spray was significantly more effective than the 5 mg oral tablet.[6]

Contraindications

Zolmitriptan is contraindicated in patients with cerebrovascular or cardiovascular disease because serotonin 5-HT1B receptors are present in coronary arteries. Such conditions include, but are not limited to, coronary artery disease, stroke, and peripheral vascular disease.[4] It is also contraindicated in hemiplegic migraine.[4]

Side effects

Side effects include neck/throat/jaw pain/tightness/pressure, dizziness, paresthesia, asthenia, somnolence, warm/cold sensations, nausea, heaviness sensation, and dry mouth.[1]

As for cardiovascular side effects, 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-related increase in sedation. There is a risk for medication withdrawal headache or medication overuse headache.[4]

Zolmitriptan has a weak affinity for serotonin 5-HT1A receptors; these receptors have been implicated in the development of serotonin syndrome.[4]

Overdose

There is limited experience with overdose of zolmitriptan and there is no specific antidote for zolmitriptan overdose.[1] A dose of zolmitriptan of 50 mg, which is 10- to 40-fold the clinically used dose range of 1.25 to 5 mg, commonly resulted in sedation in patients in a clinical study.[1] Zolmitriptan has a relatively short elimination half-life of 3 hours, and so symptoms of overdose may be expected to resolve within around 15 hours post-intake.[1]

Interactions

Following administration of the non-selective cytochrome P450 inhibitor cimetidine, the elimination half-life and total exposure of zolmitriptan and its active metabolite were approximately doubled.[4] The major metabolite of zolmitriptan, N-desmethylzolmitriptan (183C91), which is active and has several-fold greater affinity for the serotonin 5-HT1B and 5-HT1D receptors than zolmitriptan, is metabolized into an inactive form by monoamine oxidase A (MAO-A).[7] The reversible inhibitor of MAO-A (RIMA) moclobemide combined with zolmitriptan has been found to increase N-desmethylzolmitriptan exposure and peak levels by 1.5- to 3-fold.[7]

Pharmacology

Pharmacodynamics

Zolmitriptan activities
Target Affinity (Ki, nM)
5-HT1A 16–316 (Ki)
3,020–>10,000 (EC50)
55% (Emax)
5-HT1B 0.47–20 (Ki)
3.8–60 (EC50)
99–102% (Emax)
5-HT1D 0.11–4 (Ki)
0.29–1.6 (EC50)
86–106% (Emax)
5-HT1E 10–>10,000 (Ki)
6.6–62 (EC50)
101% (Emax)
5-HT1F 28–617 (Ki)
10–420 (EC50)
97% (Emax)
5-HT2A >10,000 (Ki)
>10,000 (EC50)
5-HT2B 65–>10,000 (Ki)
>10,000 (EC50)
5-HT2C 79,400 (Ki) (guinea pig)
ND (EC50)
5-HT3 >3,160 (mouse)
5-HT4 >3,160 (guinea pig)
5-HT5A 398 (rat)
5-HT6 >3,160
5-HT7 87–96 (Ki)
525 (EC50)
α1A–α1D ND
α2 79,000
α2A–α2C ND
β1–β3 ND
D1, D2 >100,000
D3–D5 ND
H1–H4 ND
M1–M5 ND
I1, I2 ND
σ1, σ2 ND
TAAR1 ND
SERT ND
NET ND
DAT ND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [8][9][10][11][12][13][14][15][16]
[17][18][19][20][21][22][23][24][25]

Zolmitriptan is a selective serotonin 5-HT1B and 5-HT1D receptor agonist with weak affinity for the serotonin 5-HT1A receptor.[10] It also has affinity for other serotonin receptors, including the serotonin 5-HT1E, 5-HT1F, 5-HT2B, 5-HT5A, and 5-HT7 receptors.[10] Conversely, its affinities for the serotonin 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, and 5-HT6 receptors are negligible or undetectable.[10][21] It is likewise inactive as a serotonin 5-HT2A receptor agonist.[21]

Zolmitriptan's major metabolite, N-desmethylzolmitriptan (183C91), is also active and has about 2- to 6-fold the affinity of zolmitriptan for the serotonin 5-HT1B and 5-HT1D receptors.[7]

Its action on serotonin 5-HT1B and 5-HT1D receptors causes vasoconstriction in intracranial blood vessels; as well it can inhibit the release of pro-inflammatory neuropeptides from trigeminal perivascular nerve endings. It crosses the blood–brain barrier as evidenced by the presence of radiolabeled zolmitriptan within the cells of the trigeminal nucleus caudalis and nucleus tractus solitarii.[4]

Pharmacokinetics

Absorption

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 2.4 L/kg after intravenous administration.[4] 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.[26]

Distribution

Zolmitriptan is a more lipophilic compound with greater central permeability than certain other triptans like sumatriptan.[27][28] It has been found to cross the blood–brain barrier and enter the central nervous system both in animals and humans.[29] In a clinical pharmacokinetic study, brain concentrations were about 20% of plasma concentrations.[30] However, in another clinical study, the drug achieved relatively low occupancy of central serotonin 5-HT1B receptors (4–5%) as measured by positron emission tomography (PET) imaging.[29][31][30]

Metabolism

Zolmitriptan is metabolized into three major metabolites by the human hepatic cytochrome P450 enzymes—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 metabolites: zolmitriptan N-oxide and an indole acetic acid derivative.[7] N-Desmethylzolmitriptan circulates at higher levels than those of zolmitriptan.[7] This metabolite is deaminated by monoamine oxidase A (MAO-A).[7]

Elimination

Zolmitriptan has an elimination half-life of about 3 hours before it undergoes renal elimination; its clearance is greater than the glomerular filtration rate suggesting that there is some renal tubular secretion of the compound.[4]

Chemistry

Zolmitriptan, also known as [(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl-N,N-dimethyltryptamine, is a tryptamine derivative and a 5-substituted derivative of the psychedelic drug dimethyltryptamine (DMT).[1][2] It is specifically the derivative of DMT in which the hydrogen atom at position 5 of the indole ring has been substituted with a [(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl group.[2]

The experimental log P of zolmitriptan is 1.6 to 1.8.[2][32] For comparison, the experimental log P of sumatriptan is 0.8 to 0.93.[33][32] Zolmitriptan is much more lipophilic than sumatriptan.[10][32]

Analogues of zolmitriptan include other triptans like sumatriptan, naratriptan, rizatriptan, eletriptan, almotriptan, and frovatriptan.[10][32]

History

Zolmitriptan was patented in 1990[3] and was first described in the scientific literature by 1994.[34][35][36] It was first introduced for medical use in the United States in 1997.[3][1][37]

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.[38]

AstraZeneca's U.S. patent on Zomig tablets expired on November 14, 2012, and its pediatric exclusivity extension expired on May 14, 2013.[39] 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.[40]

In Russia, versions of zolmitriptan which are not registered in the National registry of medications may be regarded as narcotic drugs (derivatives of dimethyltriptamine).[41]

Research

Obsessive–compulsive disorder

Zolmitriptan showed no effect on obsessive–compulsive disorder (OCD) symptoms nor on mood or anxiety in a clinical study.[42][43]

Social deficits and aggression

Zolmitriptan, in a modified-release formulation with code name ML-004 (or ML004), is under development by MapLight Therapeutics for the treatment of pervasive developmental disorders (e.g., autism), agitation, and aggression.[44][45][46][47][48][49] The drug has been found to reduce aggression in rodents[50][51][52] and has also been reported to decrease aggression in humans.[53][54] As of June 2023, zolmitriptan is in phase 2 clinical trials for pervasive developmental disorders, phase 1 clinical trials for agitation, and is in the preclinical stage of development for aggression.[44][45][46]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 "Highlights of prescribing information". https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020768s023,021231s014,021450s010lbl.pdf. 
  2. ↑ 2.0 2.1 2.2 2.3 "Zolmitriptan". https://pubchem.ncbi.nlm.nih.gov/compound/60857. 
  3. ↑ 3.0 3.1 3.2 (in en) Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 531. ISBN 978-3-527-60749-5. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA531. 
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 "Zolmitriptan". Statpearls. 2020. PMID 32491581. 50px Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
  5. ↑ "Migraine MLT-Down: An Unusual Presentation of Migraine in Patients With Aspartame-Triggered Headaches". Headache: The Journal of Head and Face Pain 41 (9): 899–901. 2001. doi:10.1046/j.1526-4610.2001.01164.x. PMID 11703479. 
  6. ↑ "Zolmitriptan for acute migraine attacks in adults". Cochrane Database Syst Rev 2014 (5). May 2014. doi:10.1002/14651858.CD008616.pub2. PMID 24848613. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 "Indolealkylamines: biotransformations and potential drug-drug interactions". AAPS J 10 (2): 242–253. June 2008. doi:10.1208/s12248-008-9028-5. PMID 18454322. "[...] the N-demethylated metabolites from zolmitriptan and eletriptan are both active at the 5-HT1B/1D sites. In particular, the N-desmethyl-zolmitriptan acts on 5-HT1B/1D receptors with an affinity about two- to six-fold of that of zolmitriptan and its steady state concentration is also higher than the parent drug. Therefore, N-desmethyl-zolmitriptan may have important contribution to the overall zolmitriptan drug effects. This active metabolite undergoes selective MAO-A-mediated deamination metabolism, resulting in an inactive indole acetic acid derivative (21) (Fig. 3). Because zolmitriptan is extensively N-demethylated and N-desmethyl-zolmitriptan is primarily excreted via deamination, potent MAO-A inhibitors are anticipated to alter the pharmacokinetics of N-desmethyl-zolmitriptan in humans. Indeed, concurrent use of selective MAO-A inhibitor, moclobemide, has been shown to cause 1.5- to 3-fold increase in the systemic exposure (AUC) and peak drug concentration (Cmax) of N-desmethyl-zolmitriptan (25).". 
  8. ↑ "BindingDB BDBM50033383 (S)-4-((3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)methyl)oxazolidin-2-one::(S)-4-[3-(2-Dimethylamino-ethyl)-1H-indol-5-ylmethyl-oxazolidin-2-one::311C90::CHEMBL1185::ZOLMITRIPTAN::ZOMIG::ZOMIG-ZMT"]. https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50033383. 
  9. ↑ "Pharmacology of triptans". Emerging Drugs 4 (1): 107–125. 1999. doi:10.1517/14728214.4.1.107. ISSN 1361-9195. 
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 "Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy". Drugs 60 (6): 1259–1287. December 2000. doi:10.2165/00003495-200060060-00003. PMID 11152011. 
  11. ↑ "Current and emerging second-generation triptans in acute migraine therapy: a comparative review". J Clin Pharmacol 40 (7): 687–700. July 2000. doi:10.1177/00912700022009431. PMID 10883409. 
  12. ↑ "Success and failure of triptans". The Journal of Headache and Pain 2 (1): 3–11. 2001. doi:10.1007/s101940170040. ISSN 1129-2369. 
  13. ↑ "Coronary Side Effects of Antimigraine Drugs From Patient to Receptor". 22 December 1999. https://repub.eur.nl/pub/16171/. "Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]" 
  14. ↑ "Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine". 13 March 2002. https://repub.eur.nl/pub/16167/. "Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]" 
  15. ↑ "Receptor specificity and trigemino-vascular inhibitory actions of a novel 5-HT1B/1D receptor partial agonist, 311C90 (zolmitriptan)". British Journal of Pharmacology 121 (2): 157–164. May 1997. doi:10.1038/sj.bjp.0701041. PMID 9154322. 
  16. ↑ "How efficacious are 5-HT1B/D receptor ligands: an answer from GTP gamma S binding studies with stably transfected C6-glial cell lines". Neuropharmacology 36 (4–5): 499–512. 1997. doi:10.1016/s0028-3908(96)00170-0. PMID 9225275. 
  17. ↑ "Computer-aided design and synthesis of 5-substituted tryptamines and their pharmacology at the 5-HT1D receptor: discovery of compounds with potential anti-migraine properties". Journal of Medicinal Chemistry 38 (18): 3566–3580. September 1995. doi:10.1021/jm00018a016. PMID 7658443. 
  18. ↑ "Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors". Journal of Medicinal Chemistry 38 (18): 3602–3607. September 1995. doi:10.1021/jm00018a020. PMID 7658447. 
  19. ↑ "Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist". Bioorganic & Medicinal Chemistry Letters 8 (6): 675–680. March 1998. doi:10.1016/s0960-894x(98)00090-0. PMID 9871581. 
  20. ↑ "Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan". Cephalalgia 30 (10): 1159–1169. October 2010. doi:10.1177/0333102410370873. PMID 20855361. 
  21. ↑ 21.0 21.1 21.2 "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology 176 (24): 4681–4695. December 2019. doi:10.1111/bph.14832. PMID 31418454. "TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]". 
  22. ↑ Perez, M.; Halazy, S.; Pauwels, P.J.; Colpaert, F.C.; John, G.W. (1999). "F-11356". Drugs of the Future 24 (6): 0605. doi:10.1358/dof.1999.024.06.537284. http://access.portico.org/stable?au=pjbf78x6c9d. Retrieved 23 June 2025. 
  23. ↑ "Lasmiditan hydrochloride". Drugs of the Future 37 (10): 709. 2012. doi:10.1358/dof.2012.037.010.1873629. ISSN 0377-8282. http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1873629&p_IsPs=N. Retrieved 19 June 2025. 
  24. ↑ "Evidence-based symptomatic treatment of migraine". Migraine Management. Handbook of Clinical Neurology. 199. 2024. pp. 203–218. doi:10.1016/B978-0-12-823357-3.00004-5. ISBN 978-0-12-823357-3. 
  25. ↑ "Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan". Headache 42 (Suppl 2): S47–S53. April 2002. doi:10.1046/j.1526-4610.42.s2.2.x. PMID 12028320. 
  26. ↑ "The absolute bioavailability and effect of food on the pharmacokinetics of zolmitriptan in healthy volunteers". British Journal of Clinical Pharmacology 46 (5): 433–439. November 1998. doi:10.1046/j.1365-2125.1998.00809.x. PMID 9833595. 
  27. ↑ "Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine". Cephalalgia 17 (Suppl 18): 4–14. October 1997. doi:10.1177/0333102497017S1802. PMID 9399012. 
  28. ↑ "Pharmacokinetic evaluation of zolmitriptan for the treatment of migraines". Expert Opin Drug Metab Toxicol 8 (8): 1043–1050. August 2012. doi:10.1517/17425255.2012.701618. PMID 22762358. 
  29. ↑ 29.0 29.1 "Serotonergic mechanisms in the migraine brain - a systematic review". Cephalalgia 37 (3): 251–264. March 2017. doi:10.1177/0333102416640501. PMID 27013238. "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.". 
  30. ↑ 30.0 30.1 "Distribution of zolmitriptan into the CNS in healthy volunteers: a positron emission tomography study". Drugs in R&D 6 (3): 139–147. 2005. doi:10.2165/00126839-200506030-00002. PMID 15869317. 
  31. ↑ "A PET study with [11C]AZ10419369 to determine brain 5-HT1B receptor occupancy of zolmitriptan in healthy male volunteers". Cephalalgia 33 (10): 853–860. July 2013. doi:10.1177/0333102413476372. PMID 23430984. 
  32. ↑ 32.0 32.1 32.2 32.3 "Medicinal chemistry of antimigraine drugs". Curr Med Chem 20 (26): 3300–3316. 2013. doi:10.2174/0929867311320260012. PMID 23746273. 
  33. ↑ "Sumatriptan". https://pubchem.ncbi.nlm.nih.gov/compound/5358. 
  34. ↑ "Joint 1994 Wolff Award Presentation. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1D receptor agonist 311C90". Headache 34 (7): 394–399. 1994. doi:10.1111/j.1526-4610.1994.hed3407394.x. PMID 7928323. 
  35. ↑ "Pre-clinical profile of the novel 5-HT 1D receptor agonist 311C90.". New Advances in Headache Research 4: 3–4. 1994. 
  36. ↑ "Clinical pharmacology of 311C90.". New Advances in Headache Research 4: 9–10. 1994. 
  37. ↑ "AstraZeneca/Burroughs Wellcome". 5 November 2023. https://adisinsight.springer.com/drugs/800002911. 
  38. ↑ "2008 Top 200 generic drugs by retail dollars". http://drugtopics.modernmedicine.com/drugtopics/data/articlestandard//drugtopics/192009/597083/article.pdf.   (332 KB). Drug Topics (May 26, 2009). Retrieved on August 25, 2009.
  39. ↑ "Generic Zomig-ZMT Availability". https://www.drugs.com/availability/generic-zomig-zmt.html. 
  40. ↑ "Migraine treatment Zolmitriptan launched by Actavis in Europe". http://www.actavis.com/en/media+center/newsroom/articles/migraine_zolmitriptan_eu.htm. 
  41. ↑ "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)". Гарант. http://base.garant.ru/12112176/. "ДМТ (диметилтриптамин) и его производные, за исключением производных, включенных в качестве самостоятельных позиций в перечень" 
  42. ↑ "The 5-HT1B receptor - a potential target for antidepressant treatment". Psychopharmacology (Berl) 235 (5): 1317–1334. May 2018. doi:10.1007/s00213-018-4872-1. PMID 29546551. 
  43. ↑ "Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder". Psychopharmacology (Berl) 152 (1): 74–79. September 2000. doi:10.1007/s002130000529. PMID 11041318. 
  44. ↑ 44.0 44.1 "ML 004". 8 June 2023. https://adisinsight.springer.com/drugs/800061291. 
  45. ↑ 45.0 45.1 "Delving into the Latest Updates on ML-004 with Synapse". 28 September 2024. https://synapse.patsnap.com/drug/64e037a51d55415f8f4919a04aef3082. 
  46. ↑ 46.0 46.1 "Going on Trial: Serotonin drug; psilocybin phase 2; placebo response data". 28 April 2023. https://www.thetransmitter.org/spectrum/going-on-trial-serotonin-drug-psilocybin-phase-2-placebo-response-data/. 
  47. ↑ "TAAR1 and 5-HT1B receptor agonists attenuate autism-like irritability and aggression in rats prenatally exposed to valproic acid". Pharmacol Biochem Behav 245. August 2024. doi:10.1016/j.pbb.2024.173862. PMID 39197535. "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).". 
  48. ↑ "Maplight Autism Study". https://www.corticacare.com/research/maplight. "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." 
  49. ↑ "Zolmitriptan by MapLight therapeutics for Autism Spectrum Disorder (ASD): Likelihood of Approval". https://www.pharmaceutical-technology.com/data-insights/zolmitriptan-maplight-therapeutics-autism-spectrum-disorder-asd-likelihood-of-approval/. 
  50. ↑ "Drugs and aggression". Recent Pat CNS Drug Discov 3 (1): 40–49. January 2008. doi:10.2174/157488908783421456. PMID 18221240. "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].". 
  51. ↑ "5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis". Eur J Pharmacol 526 (1–3): 125–139. December 2005. doi:10.1016/j.ejphar.2005.09.065. PMID 16310183. "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).". 
  52. ↑ "Zolmitriptan--a 5-HT1B/D agonist, alcohol, and aggression in mice". Psychopharmacology (Berl) 157 (2): 131–141. September 2001. doi:10.1007/s002130100778. PMID 11594437. 
  53. ↑ "Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology". Psychopharmacology (Berl) 238 (6): 1417–1436. June 2021. doi:10.1007/s00213-021-05787-x. PMID 33694032. "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).". 
  54. ↑ "Zolmitriptan and human aggression: interaction with alcohol". Psychopharmacology (Berl) 210 (4): 521–531. July 2010. doi:10.1007/s00213-010-1851-6. PMID 20407761. 

Further reading



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