Mesulergine

{{Short description|Chemical compound}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | UNII_Ref = {{fdacite|correct|FDA}} | UNII = SML95FK06I | verifiedrevid = 462249130 | IUPAC_name = ''N''<nowiki>'</nowiki>-(1,6-dimethylergolin-8α-yl)-''N'',''N''-dimethylsulfamide | image = Mesulergine.svg | image_class = skin-invert-image | width = 175px | class = Dopamine agonist | index_label = | index2_label = [³H]mesulergine | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C18H26N4O2S/c1-20(2)25(23,24)19-13-9-15-14-6-5-7-16-18(14)12(10-21(16)3)8-17(15)22(4)11-13/h5-7,10,13,15,17,19H,8-9,11H2,1-4H3/t13-,15+,17+/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = JLVHTNZNKOSCNB-YSVLISHTSA-N | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 64795-35-3 | ATC_prefix = | ATC_suffix = | PubChem = 68848 | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 73378 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 462903 | IUPHAR_ligand2 = 232 | IUPHAR_ligand = 206 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 62081 | synonyms = CU-32085 | C = 18 | H = 26 | N = 4 | O = 2 | S = 1 | smiles = O=S(=O)(N(C)C)N[C@H]2C[C@@H]3c4cccc1c4c(cn1C)C[C@H]3N(C2)C | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | pregnancy_category = | legal_status = | routes_of_administration = }}

'''Mesulergine''' ({{Abbrlink|INN|International Nonproprietary Name}}) (developmental code name '''CU-32085''') is a drug of the ergoline group which was never marketed.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA776|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=776–}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA177|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=177–}}</ref>

==Pharmacology== ===Pharmacodynamics=== {| class="wikitable floatleft" style="font-size:small;" |+ {{Nowrap|Mesulergine activities}} |- ! Target !! Affinity (K_i, nM) !! Species |- | 5-HT_1A || 195–398 || Human |- | 5-HT_1B || 631–1,288 || Human |- | 5-HT_1D || 1,700–>10,000 || Human |- | 5-HT_1E || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | 5-HT_1F || >10,000 || Human |- | 5-HT_2A || 19.5–151 || Human |- | 5-HT_2B || 1.44–3.62 || Human |- | 5-HT_2C || 1.12–48.5 || Human |- | 5-HT₃ || >10,000 || Rat |- | 5-HT₄ || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} |- | 5-HT_5A || 1,000 || Rat |- | 5-HT_5B || 1,000 || Rat |- | 5-HT₆ || 776–3,800 || Human |- | 5-HT₇ || 7.9–31.6 || Human |- | D₂ || 8–12 || Rat |- class="sortbottom" | colspan="3" style="width: 1px; background-color:var(--background-color-notice-subtle,#eaecf0); color:inherit; text-align: center;" | '''Notes:''' The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. '''Refs:'''<ref name="PDSPKiDatabase">{{cite web | title=Kᵢ Database | website=PDSP | date=25 June 2025 | url=https://pdspdb.unc.edu/kidb2/kidb/web/kis-results/index?KisResultsSearch%5Binput_receptors%5D=&KisResultsSearch%5Binput_sources%5D=&KisResultsSearch%5Binput_species%5D=&KisResultsSearch%5Binput_hot_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D=&KisResultsSearch%5Binput_test_ligands%5D%5B%5D=1206&KisResultsSearch%5Binput_citations%5D=&KisResultsSearch%5BsearchType%5D=&KisResultsSearch%5Bki_val_from%5D=&KisResultsSearch%5Bki_val_to%5D=&KisResultsSearch%5Bcustom_ki_val%5D= | access-date=25 June 2025}}</ref><ref name="BindingDB">{{cite web | title= | website=BindingDB | url=https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50024204&submit=repeat&energyterm=&column=KI&startPg=50&Increment=50 | access-date=25 June 2025}}</ref><ref name="Markstein1983">{{cite journal | vauthors = Markstein R | title = Mesulergine and its 1,20-N,N-bidemethylated metabolite interact directly with D1- and D2-receptors | journal = Eur J Pharmacol | volume = 95 | issue = 1–2 | pages = 101–107 | date = November 1983 | pmid = 6230246 | doi = 10.1016/0014-2999(83)90272-8 | url = }}</ref><ref name="DumuisBouhelalSebben1988">{{cite journal | vauthors = Dumuis A, Bouhelal R, Sebben M, Cory R, Bockaert J | title = A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system | journal = Mol Pharmacol | volume = 34 | issue = 6 | pages = 880–887 | date = December 1988 | pmid = 2849052 | doi = 10.1016/S0026-895X(25)10130-2| url = }}</ref> |}

Mesulergine acts on serotonin and dopamine receptors.<ref name="pmid6855451">{{cite journal | vauthors = Closse A | title = [3H]Mesulergine, a selective ligand for serotonin-2 receptors | journal = Life Sciences | volume = 32 | issue = 21 | pages = 2485–2495 | date = May 1983 | pmid = 6855451 | doi = 10.1016/0024-3205(83)90375-2 }}</ref><ref name="pmid6230246">{{cite journal | vauthors = Markstein R | title = Mesulergine and its 1,20-N,N-bidemethylated metabolite interact directly with D1- and D2-receptors | journal = European Journal of Pharmacology | volume = 95 | issue = 1–2 | pages = 101–107 | date = November 1983 | pmid = 6230246 | doi = 10.1016/0014-2999(83)90272-8 }}</ref><ref name="Glennon1987">{{cite journal | vauthors = Glennon RA | title = Central serotonin receptors as targets for drug research | journal = J Med Chem | volume = 30 | issue = 1 | pages = 1–12 | date = January 1987 | pmid = 3543362 | doi = 10.1021/jm00384a001 | url = | quote = Table II. Affinities of Selected Phenalkylamines for 5-HT1 and 5-HT2 Binding Sites}}</ref> Specifically, it is an agonist of dopamine D₂-like receptors and serotonin 5-HT₆ receptors and an antagonist of serotonin 5-HT_2A, 5-HT_2B, 5-HT_2C, and 5-HT₇ receptors.<ref name="Glennon1987" />{{Additional citation needed|date=April 2021}} It also has affinity for the 5-HT_1A, 5-HT_1B, 5-HT_1D, 5-HT_1F, and 5-HT_5A receptors.<ref name="PDSDKiDB">National Institute of Mental Health. PDSD Ki Database (Internet). ChapelHill (NC): University of North Carolina. Available from: {{cite web|url=http://pdsp.med.unc.edu/pdsp.php|title=PDSP Database - UNC |access-date=|url-status=|archive-url=https://web.archive.org/web/20210412230434/https://pdsp.unc.edu/databases/pdsp.php?receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=Mesulergine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query |archive-date=12 April 2021}}</ref><ref name="Glennon1987" />

==Research== Mesulergine had entered clinical trials for the treatment of Parkinson's disease; however, further development was halted due to adverse histological abnormalities in rats.<ref name="pmid3517235">{{cite journal | vauthors = Dupont E, Mikkelsen B, Jakobsen J | title = Mesulergine in early Parkinson's disease: a double blind controlled trial | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 49 | issue = 4 | pages = 390–395 | date = April 1986 | pmid = 3517235 | pmc = 1028763 | doi = 10.1136/jnnp.49.4.390 }}</ref> It was also investigated for the treatment of hyperprolactinemia (high prolactin levels).<ref name="pmid12808385">{{cite journal | vauthors = Bankowski BJ, Zacur HA | title = Dopamine agonist therapy for hyperprolactinemia | journal = Clinical Obstetrics and Gynecology | volume = 46 | issue = 2 | pages = 349–362 | date = June 2003 | pmid = 12808385 | doi = 10.1097/00003081-200306000-00013 | s2cid = 29368668 }}</ref>

==See also== * Disulergine * Etisulergine * Quinagolide

==References== {{Reflist}}

{{Dopamine receptor modulators}} {{Serotonin receptor modulators}} {{Ergolines}}

Category:5-HT6 agonists Category:Abandoned drugs Category:Dopamine agonists Category:Ergolines Category:Prolactin inhibitors Category:Serotonin receptor antagonists Category:Sulfamides