Pipamazine (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

; trade names Mornidine, Mometine, Nausidol) is a drug of the

phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...

class formerly used as an antiemetic. It is chemically related to chlorpromazine, but has negligible

antipsychotic Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...

activity and produces few

extrapyramidal side effects Extrapyramidal symptoms (EPS) are symptoms that are archetypically associated with the extrapyramidal system of the brain's cerebral cortex. When such symptoms are caused by medications or other drugs, they are also known as extrapyramidal side ...

. Pipamazine was introduced to the U.S. market in 1959 by G. D. Searle & Company. It was advertised for

morning sickness Morning sickness, also called nausea and vomiting of pregnancy (NVP), is a symptom of pregnancy that involves nausea or vomiting. Despite the name, nausea or vomiting can occur at any time during the day. Typically the symptoms occur between th ...

and

postoperative nausea and vomiting Postoperative nausea and vomiting (PONV) is the phenomenon of nausea, vomiting, or retching experienced by a patient in the postanesthesia care unit (PACU) or within 24 hours following a surgical procedure. PONV affects about 10% of the population ...

, and was claimed to reduce the need for postoperative analgesia. Advertisement. It was eventually withdrawn from the U.S. market in 1969, after reports of hepatotoxicity (liver injury). 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.

Adverse effects

Mornidine advertisements for postoperative recovery claimed "unusually low side effects". However, contemporary comparative trials found that

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dias ...

(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. 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.

Synthesis

The alkylation of 2-chloro-10-(3-chloropropyl)phenothiazine 765-59-5(1) with Isonipecotamide 9546-32-2(2) gives pipamazine (3).

References

{{Antiemetics and antinauseants Antiemetics Hepatotoxins Phenothiazines Piperidines Withdrawn drugs