Pipamazine

Pipamazine

Clinical data
Pregnancy category	Formerly used for morning sickness
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Legal status	Withdrawn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	84-04-8
PubChem CID	6761
ChemSpider	6503
UNII	653552FH1N
KEGG	D02606
ChEBI	CHEBI:135641
ChEMBL	ChEMBL1909072
CompTox Dashboard (EPA)	DTXSID3023477
ECHA InfoCard	100.001.375
Chemical and physical data
Formula	C21H24ClN3OS
Molar mass	401.95 g·mol−1
3D model (JSmol)	Interactive image
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 (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 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 ^[3] It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury).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:

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. Archived from the original (PDF) on 2011-07-06. Retrieved 2010-09-28.
2. [No authors listed] (July 1959). "Now she can cook breakfast again..." Canadian Medical Association Journal . 81 (1): 59. PMC   1830735 . Advertisement.
3. [No authors listed] (April 1960). "Lessened postoperative vomiting with MORNIDINE". 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).