Pipamazine

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.[1]

Pipamazine
Clinical data
Pregnancy
category
Routes of
administration		Oral, intramuscular injection
ATC code
  • None
Legal status
Legal status
  • Withdrawn
Identifiers
IUPAC name
  • 1-[3-(2-chlorophenothiazin-10-yl)propyl]piperidine-4-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.001.375
Chemical and physical data
FormulaC21H24ClN3OS
Molar mass401.95 g·mol−1
3D model (JSmol)
SMILES
  • C1CN(CCC1C(=O)N)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)Cl
InChI
  • InChI=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)
  • Key:OSJJYEUEJRVVOD-UHFFFAOYSA-N
 NY (what is this?)  (verify)

Pipamazine was introduced to the U.S. market in 1959 by G. D. Searle & Company. It was advertised for morning sickness[2] and postoperative nausea and vomiting, and was claimed to reduce the need for postoperative analgesia.[3] It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury).[4][5]

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.[1]

Adverse effects

Mornidine advertisements for postoperative recovery claimed "unusually low side effects".[3] 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.[6] 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.[7]

Synthesis
Thieme Patents:[8][9]

The alkylation of 2-chloro-10-(3-chloropropyl)phenothiazine [2765-59-5] (1) with Isonipecotamide [39546-32-2] (2) gives pipamazine (3).

References
  1. Frota LH (2003). Cinqüenta anos de medicamentos antipsicóticos em psiquiatria (PDF) (in Portuguese) (1st ed.). Rio de Janeiro: UFRJ. p. 486. ISBN 85-903827-1-0.
  2. [No authors listed] (July 1959). "Now she can cook breakfast again..." (PDF). Canadian Medical Association Journal. 81 (1): 59. PMC 1830735. Advertisement.
  3. [No authors listed] (April 1960). "Lessened postoperative vomiting with MORNIDINE" (PDF). Annals of Surgery. 151 (4). PMC 1613578. Advertisement.
  4. 34 FR 12051. July 17, 1969.
  5. Wysowski DK, Swartz L (June 2005). "Adverse drug event surveillance and drug withdrawals in the United States, 1969-2002: the importance of reporting suspected reactions". Archives of Internal Medicine. 165 (12): 1363–9. doi:10.1001/archinte.165.12.1363. PMID 15983284.
  6. Blatchford E (March 1961). "Studies of anti-emetic drugs: A comparative study of cyclizine (Marzine), pipamazine (Mornidine), trimethobenzamide (Tigan), and hyoscine". Canadian Journal of Anesthesia. 8 (2): 159–65. doi:10.1007/BF03021345.
  7. Healy D (2002). "Explorations in a new world". The creation of psychopharmacology. Cambridge: Harvard University Press. pp. 123–4. ISBN 0-674-01599-1.
  8. John W Cusic, Dr Henry William Sause, DE 1089386 (1960 to Searle & Co).
  9. John W Cusic, Sause Henry William, U.S. Patent 2,957,870 (1960 to Searle & Co).
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