Solypertine
{{Short description|Abandoned sympatholytic drug}}
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| CAS_number = 4448-96-8
| CAS_supplemental =
5591-43-5 (tartrate)
| PubChem = 20517
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| ChemSpiderID = 19323
| UNII = 9BUF6DCO0C
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| ChEMBL = 1739674
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| synonyms = Solipertine; WIN18413; WIN-18,413; Win-18413; WIN 18413-2
| IUPAC_name = 7-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-5H-[1,3]dioxolo[4,5-f]indole
| C=22 | H=25 | N=3 | O=3
| SMILES = COC1=CC=CC=C1N2CCN(CC2)CCC3=CNC4=CC5=C(C=C43)OCO5
| StdInChI = 1S/C22H25N3O3/c1-26-20-5-3-2-4-19(20)25-10-8-24(9-11-25)7-6-16-14-23-18-13-22-21(12-17(16)18)27-15-28-22/h2-5,12-14,23H,6-11,15H2,1H3
| StdInChIKey = GIWODWVYEOAGQV-UHFFFAOYSA-N
}}
Solypertine ({{Abbrlink|INN|International Nonproprietary Name}}; developmental code name WIN-18413), also known as solypertine tartrate ({{Abbrlink|USAN|United States Adopted Name}}) in the case of the tartrate salt, is a drug of the pertine group described as an antiadrenergic (or adrenolytic/sympatholytic) and as also potentially possessing neuroleptic properties which was never marketed.{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1105 | access-date=30 October 2024 | page=1105}}{{cite book | vauthors = Negwer M | title=Organic-chemical Drugs and Their Synonyms: (an International Survey) | publisher=Akademie Verlag | year=1994 | isbn=978-3-05-500156-7 | url=https://books.google.com/books?id=ywltAAAAMAAJ&q=solypertine | access-date=30 October 2024 | page=2064}}{{cite book | author=National Institutes of Health (U.S.) | author2=National Cancer Institute (U.S.) | title=Cancer Treatment Reports | publisher=U.S. Department of Health, Education, and Welfare, Public Health Service, National Institutes of Health | series=DHEW publication | issue=v. 62, no. 1 | year=1978 | url=https://books.google.com/books?id=BmUVaDSUkXQC&pg=PA58 | access-date=30 October 2024 | page=58}}{{cite book | author=Psychopharmacology Service Center (U.S.) | title=Psychopharmacology Abstracts | publisher=U.S. Department of Health, Education, and Welfare, Public Health Service | series=DHEW publication | year=1962 | issn=0033-3166 | url=https://books.google.com/books?id=_x4kIURvqacC&pg=PA972 | access-date=30 October 2024 | page=972}}{{cite journal | vauthors = Wylie DW, Archer S | title = Structure-Activity Relationships of 1-[3-Indolyl)alkyl]-4-arylpiperazines. A New Series of Tranquilizers | journal = Journal of Medicinal and Pharmaceutical Chemistry | volume = 5 | issue = 5 | pages = 932–943 | date = September 1962 | pmid = 14056437 | doi = 10.1021/jm01240a006 | publisher = American Chemical Society (ACS) }}
Structurally, it is a substituted tryptamine and a piperazinylethylindole.{{cite book | vauthors = Ellis GP, Luscombe DK | title=Progress in Medicinal Chemistry | publisher=Elsevier Science | issue=v. 33 | year=1996 | isbn=978-0-08-086281-1 | url=https://books.google.com/books?id=SDaZ4qcemf8C&pg=PA219 | access-date=30 October 2024 | page=219 | quote=Pertines (class 7; Table 5.12) The pertines oxypertine, solypertine, milipertine, and alpertine are piperazinylethylindoles.}} The drug is closely structurally related to other "pertines" including alpertine, milipertine, and oxypertine, which are also tryptamines and piperazinylethylindoles. Solypertine can be synthesized from 5,6-methylenedioxyindole.{{cite book | vauthors = Ishar MP, Faruk A | title=Syntheses of Organic Medicinal Compounds | publisher=Alpha Science | year=2006 | isbn=978-1-84265-280-0 | url=https://books.google.com/books?id=CK31Zjf-UWMC&pg=PA48 | access-date=30 October 2024 | page=48}}
The related drug oxypertine shows high affinity for the serotonin 5-HT2 and dopamine D2 receptors (Ki = 8.6{{nbsp}}nM and 30{{nbsp}}nM, respectively) and is also known to act as a catecholamine depleting agent.{{cite book | vauthors = Megens AA, Kennis LE | title = Risperidone and related 5HT2/D2 antagonists: a new type of antipsychotic agent? | volume = 33 | pages = 185–232 | date = 1996 | pmid = 8776944 | doi = 10.1016/s0079-6468(08)70306-0 | isbn = 978-0-444-82310-6 | series = Progress in Medicinal Chemistry }}{{cite journal | vauthors = Bak IJ, Hassler R, Kim JS | title = Differential monoamine depletion by oxypertine in nerve terminals. Granulated synaptic vesicles in relation to depletion of norepinephrine, dopamine and serotonin | journal = Zeitschrift für Zellforschung und Mikroskopische Anatomie | volume = 101 | issue = 3 | pages = 448–462 | year = 1969 | pmid = 5362847 | doi = 10.1007/BF00335580 | s2cid = 32583722 }} Oxypertine, milipertine, and solypertine all antagonize the behavioral effects of tryptamine, a serotonin receptor agonist, and apomorphine, a dopamine receptor agonist, in animals.{{cite journal | vauthors = Niemegeers CJ, Janssen PA | title = A systematic study of the pharmacological activities of dopamine antagonists | journal = Life Sciences | volume = 24 | issue = 24 | pages = 2201–2216 | date = June 1979 | pmid = 388130 | doi = 10.1016/0024-3205(79)90096-1 | publisher = Elsevier BV }} ortho-Methoxyphenylpiperazine (oMeOPP) has been said to be a metabolite of milipertine and oxypertine.{{cite journal | vauthors = Elliott S | title = Current awareness of piperazines: pharmacology and toxicology | journal = Drug Testing and Analysis | volume = 3 | issue = 7–8 | pages = 430–438 | date = 2011 | pmid = 21744514 | doi = 10.1002/dta.307 | quote = Furthermore, oMeOPP is a metabolite of some prescribed drugs: enciprazione, milipertine, urapidil, dropropizine and oxypertine.[1,47] }}{{cite journal | vauthors = Caccia S, Notarnicola A, Fong MH, Benfenati E | title = Identification and quantitation of 1-arylpiperazines, metabolites resulting from side-chain cleavage of (4-substituted aryl-1-piperazinyl)alkyl heterocyclic derivatives in rat plasma and brain | journal = Journal of Chromatography | volume = 283 | issue = | pages = 211–221 | date = January 1984 | pmid = 6707118 | doi = 10.1016/s0021-9673(00)96256-3 }}
Solypertine was first described in the scientific literature by 1962.{{cite book | vauthors = Gordon M | title=Psychopharmacological Agents | publisher=Academic Press | series=Medicinal chemistry | year=2013 | isbn=978-1-4832-7446-1 | url=https://books.google.com/books?id=0SwXBQAAQBAJ&pg=PA297 | access-date=30 October 2024 | page=297}}