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	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Legal status	Withdrawn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 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nausea and vomiting, and was claimed to reduce the need for postoperative analgesia.^[3] It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury).^[4][5]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).