Pipamazine

Pipamazine

Systematic (IUPAC) name
1-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]piperidine-4-carboxamide
Clinical data
Pregnancy cat.	Formerly used for morning sickness
Legal status	Withdrawn
Routes	Oral, intramuscular injection
Identifiers
CAS number	84-04-8
ATC code	None
PubChem	CID 6761
ChemSpider	6503 Y
UNII	653552FH1N Y
KEGG	D02606 Y
Chemical data
Formula	C21H24ClN3OS
Mol. mass	401.95 g/mol
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) Y Key:OSJJYEUEJRVVOD-UHFFFAOYSA-N Y
Y(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nausea and vomiting, and was claimed to reduce the need for postoperative analgesia.^[3] It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury).^[4][5]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]

References

1. ^ ^{a b} Frota LH (2003) (in Portuguese). Cinqüenta anos de medicamentos antipsicóticos em psiquiatria. Rio de Janeiro: UFRJ. pp. 486. ISBN 8590382710. http://www.medicina.ufrj.br/cursos/LH%20FROTA%20-%201%20Ed%20-%2050%20ANOS%20DE%20MEDICAMENTOS%20ANTIPSICOTICOS.pdf. 
2. ^ [No authors listed] (July 1959). "Now she can cook breakfast again..." (PDF). Canadian Medical Association Journal 81 (1): 59. PMC 1830735. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1830735.  Advertisement.
3. ^ ^{a b} [No authors listed] (April 1960). "Lessened postoperative vomiting with MORNIDINE^®" (PDF). Annals of Surgery 151 (4). PMC 1613578. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1613578.  Advertisement.
4. ^ 34 F.R. 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.