pipamazine
{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 451564309
| image = Pipamazine.svg
| alt = Chemical structure of Pipamazine
| tradename =
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category = Formerly used for morning sickness
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status = Withdrawn
| routes_of_administration = Oral, intramuscular injection
| ATC_prefix = None
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number = 84-04-8
| CAS_supplemental =
| PubChem = 6761
| IUPHAR_ligand =
| DrugBank =
| ChemSpiderID = 6503
| UNII = 653552FH1N
| KEGG = D02606
| ChEBI = 135641
| ChEMBL = 1909072
| NIAID_ChemDB =
| PDB_ligand =
| IUPAC_name = 1-[3-(2-chlorophenothiazin-10-yl)propyl]piperidine-4-carboxamide
| C=21 | H=24 | Cl=1 | N=3 | O=1 | S=1
| SMILES = C1CN(CCC1C(=O)N)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)Cl
| StdInChI = 1S/C21H24ClN3OS/c22-16-6-7-20-18(14-16)25(17-4-1-2-5-19(17)27-20)11-3-10-24-12-8-15(9-13-24)21(23)26/h1-2,4-7,14-15H,3,8-13H2,(H2,23,26)
| StdInChIKey = OSJJYEUEJRVVOD-UHFFFAOYSA-N
}}
Pipamazine (INN; trade names Mornidine, Mometine, Nausidol) is a drug of the phenothiazine class formerly used as an antiemetic. It is chemically related to chlorpromazine, but has negligible antipsychotic activity and produces few extrapyramidal side effects.{{cite book |vauthors=Frota LH |title=Cinqüenta anos de medicamentos antipsicóticos em psiquiatria |edition=1st |language=Portuguese |isbn=85-903827-1-0 |location=Rio de Janeiro |publisher=UFRJ |year=2003 |pages=486 |url=http://www.medicina.ufrj.br/cursos/LH%20FROTA%20-%201%20Ed%20-%2050%20ANOS%20DE%20MEDICAMENTOS%20ANTIPSICOTICOS.pdf |access-date=2010-09-28 |archive-date=2011-07-06 |archive-url=https://web.archive.org/web/20110706163929/http://www.medicina.ufrj.br/cursos/LH%20FROTA%20-%201%20Ed%20-%2050%20ANOS%20DE%20MEDICAMENTOS%20ANTIPSICOTICOS.pdf |url-status=dead }}
Pipamazine was introduced to the U.S. market in 1959 by G. D. Searle & Company. It was advertised for morning sickness{{cite journal |author=[No authors listed] |title=Now she can cook breakfast again... |journal=Canadian Medical Association Journal |volume=81 |issue=1 |date=July 1959 |pages=59 |pmc=1830735}} Advertisement. and postoperative nausea and vomiting, and was claimed to reduce the need for postoperative analgesia.{{cite journal |author=[No authors listed] |title=Lessened postoperative vomiting with MORNIDINE |journal=Annals of Surgery |volume=151 |issue=4 |date=April 1960 |pmc=1613578}} Advertisement.
It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury).{{Federal Register|34|12051}}. July 17, 1969.{{cite journal | vauthors = Wysowski DK, Swartz L | title = Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reporting suspected reactions | journal = Archives of Internal Medicine | volume = 165 | issue = 12 | pages = 1363–9 | date = June 2005 | pmid = 15983284 | doi = 10.1001/archinte.165.12.1363 | doi-access = free }}
There is very little published information on pipamazine; it is mostly absent from modern-day sources, apart from a few passing mentions in the pharmacological literature.
Adverse effects
Mornidine advertisements for postoperative recovery claimed "unusually low side effects". However, contemporary comparative trials found that hypotension (low blood pressure) was a substantial concern when the drug was given at normal dosages for this indication; blood pressure reductions of up to 70 mmHg were reported.{{cite journal | vauthors = Blatchford E |title=Studies of anti-emetic drugs: A comparative study of cyclizine (Marzine), pipamazine (Mornidine), trimethobenzamide (Tigan), and hyoscine |journal=Canadian Journal of Anesthesia |volume=8 |issue=2 |pages=159–65 |date=March 1961 |doi=10.1007/BF03021345|doi-access=free }} Reductions in dosage mitigated hypotension while maintaining antiemetic efficacy.
In his book The Creation of Psychopharmacology, Irish psychiatrist David Healy states that the failure of pipamazine to perform as a neuroleptic and its negative side effect profile helped Searle lose interest in the antipsychotic sector, and contributed to the company's refusal to market haloperidol in the United States.{{cite book | vauthors = Healy D |chapter=Explorations in a new world |title=The creation of psychopharmacology |publisher=Harvard University Press |location=Cambridge |year=2002 |pages=123–4 |isbn=0-674-01599-1}}
Synthesis
The alkylation of 2-chloro-10-(3-chloropropyl)phenothiazine [2765-59-5] (1) with Isonipecotamide [39546-32-2] (2) gives pipamazine (3).
References
{{Reflist}}
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{{Antiemetics and antinauseants}}