Prochlorperazine

Prochlorperazine (Compazine, Stemzine, Buccastem, Stemetil, Phenotil) is a dopamine (D2) receptor antagonist that belongs to the phenothiazine class of antipsychotic agents that are used for the antiemetic treatment of nausea and vertigo. It is also a highly-potent typical antipsychotic, 10-20x more potent than chlorpromazine. It is also used to treat migraine headaches. Intravenous administration can be used to treat status migrainosus.

Indications
Prochlorperazine is a phenothiazine drug. Most drugs in this category are used as anti-psychotics (neuroleptics). Neuroleptic means "nerve seizing," and describes the semi-paralyzing effect these drugs have on the brain and nervous system. Stemetil is no longer being manufactured for sale in Canada as an anti-psychotic, but it is still available for treatment of nausea, etc.

It is now relatively seldom used for the treatment of psychosis and the manic phase of bipolar disorder. It has a prominent antiemetic/antivertiginoic activity and is most often used for the (short-time) treatment of nausea and vomiting and vertigo as follows:


 * 1) To alleviate the symptoms of vertigo
 * 2) As an antiemetic, particularly for nausea and vomiting caused by chemotherapy, radiation therapy and in the pre- and postoperative setting
 * 3) In the UK, prochlorperazine maleate is available as Buccastem M in buccal form as an over-the-counter treatment for migraine. In this indication it blocks the chemoreceptor trigger zone (CTZ) in the brain, which is responsible for causing severe nausea and vomiting. Its OTC use is strictly restricted to a maximum of 2 days, because of the potentially severe side effects of prochlorperazine, which mandate supervision by a health care provider.
 * 4) In the UK prochlorperazine maleate has been prescribed to alleviate the symptoms of labyrinthitis, which include not only nausea and vertigo, but spatial and temporal 'jerking' and distortion

Formulations and pharmacokinetics
Prochlorperazine is available as an oral liquid, tablets, cream for trans dermal(compounding pharmacy), and suppositories, as well as in an injectable form.

Following intramuscular injection the antiemetic action is evident within 5 to 10 minutes and lasts for 3 to 4 hours. Rapid action is also noted after buccal treatment. With oral dosing the start of action is delayed but the duration somewhat longer (approximately 6 hours).

It is available in Egypt under the brand name Emedrotec buccal adhesive tablets by Eva pharma.

There is an inhaled form of prochlorperazine under development by Alexza Pharmaceuticals, currently in Phase II clinical trials.

Side effects
Hypersensitivities to prochlorperazine can occur and there is cross-reactivity with other drugs in the phenothiazine class. Symptoms of a reaction include dyskinesia (unusual, uncontrollable body or face movements, including abnormal movements of the tongue, also known as dystonia), seizures and seizure-like symptoms in individuals who have never had a seizure before. Long-term delay of medical treatment can lead to long-term effects. In extreme cases, it has been known to produce permanent damage to the lower jaw and the jaw joint due to extended seizure symptoms.

Prochlorperazine can also cause a life-threatening condition called neuroleptic malignant syndrome (NMS). Some symptoms of NMS include: A high fever, stiff muscles, confusion, irregular pulse or blood pressure, a fast heart rate (tachycardia), sweating, irregular heart rhythms (arrhythmias). VA and FDA research shows injection site reaction. This product has caused reported permanent arm circulatory damage when used as an i.v. push drug in conjunction with benedryl in an emergency room setting for off label use for migraine headache. (as early as 1993,patient Scott Wergin, Eureka MH, IL.) (Reaction with the blood was visible in a 2" length of vein through the skin) Mr.Wergin is available for comment in Saint Paul, MN.

Chemistry
Prochlorpherazine (2-chloro-10-[3-(4-methyl-1-piperazinyl) propyl]-phenothiazine) is prepared by the alkylation of 2-chlorophenothiazine using 4-methyl-1-piperazinyl)propyl-3-chloride in the presence of sodamide, or alkylation of 2-chloro-10-[(3-chloropropyl)]phenothiazine using 1-methylpiperazine.
 * R.J. Horclois, (1959).
 * R.J. Horclois, (1957).
 * R.J. Horclois, (1955).
 * R.J. Horclois, (1959).