Pipamazine Explained

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nausea and vomiting, and was claimed to reduce the need for postoperative analgesia.[3] It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury).[4] [5]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

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

Notes and References

  1. Book: Frota LH . Cinqüenta anos de medicamentos antipsicóticos em psiquiatria . 1st . Portuguese . 85-903827-1-0 . Rio de Janeiro . UFRJ . 2003 . 486 . 2010-09-28 . 2011-07-06 . https://web.archive.org/web/20110706163929/http://www.medicina.ufrj.br/cursos/LH%20FROTA%20-%201%20Ed%20-%2050%20ANOS%20DE%20MEDICAMENTOS%20ANTIPSICOTICOS.pdf . dead .
  2. [No authors listed] . Now she can cook breakfast again... . . 81 . 1 . July 1959 . 59 . 1830735. Advertisement.
  3. [No authors listed] . Lessened postoperative vomiting with MORNIDINE . . 151 . 4 . April 1960 . 1613578. Advertisement.
  4. . July 17, 1969.
  5. Wysowski DK, Swartz L . 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 . June 2005 . 15983284 . 10.1001/archinte.165.12.1363 . free .
  6. Blatchford E . 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 . March 1961 . 10.1007/BF03021345. free .
  7. Book: Healy D . Explorations in a new world . The creation of psychopharmacology . Harvard University Press . Cambridge . 2002 . 123–4 . 0-674-01599-1.