プロクロルペラジン

DEA NFLIS-Drug Category -> Depressants and Tranquilizers

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

log Kow = 4.88

4.6

4.79

Freely soluble in alcohol, ether, chloroform

In water, 1.496X10-2 g/L (14.96 mg/L) at 24 °C

1.10e-02 g/L

Breast Feeding; Lactation; Milk, Human; Antiemetics; Phenothiazines; Gastrointestinal Agents

FDA approved drugs -> Active ingredient

Pharmaceuticals

228 °C

228 °C

8.1

pKa = 8.1

Minute crystals; Solubility in water: less than 0.1% at 20 °C; slightly soluble in methanol, ethanol; practically insoluble in ether, benzene, chloroform; MP: 228 °C /Prochlorperazine dimaleate/

White to very light yellow crystalline powder; 1 g is soluble in about 2 mL water, in about 1500 mL alcohol; insoluble in ether, chloroform; odorless; solutions are acidic to litmus /Edisylate/

White or pale yellow crystalline powder; almost completely odorless; saturated solution is acidic to litmus; practically insoluble in water and ethanol; slightly soluble in warm chloroform /Dimaleate/

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P263, P264, P270, P271, P280, P301+P317, P304+P340, P318, P319, P330, P403+P233, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine edisylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prochlorperazine edisylate/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine maleate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prochlorperazine maleate/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Prochlorperazine dimaleate is included on this list. /Prochlorperazine dimaleate/

For more FDA Requirements (Complete) data for Prochlorperazine (9 total), please visit the HSDB record page.

May cause irritation /to the eyes, skin, and mucous membranes/. Avoid inhalation. Remove to fresh air. Avoid contact. Flush /eyes/ with copious quantities of water for at least 15 minutes. Avoid /skin/ contact. Flush with copious quantities of soap and water.

Prochlorperazine edisylate injection is physically and/or chemically incompatible with some drugs, but the compatibility depends on several factors (eg, concentrations of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.

As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Commercially available preparations of prochlorperazine should be stored in tight, light-resistant containers. Prochlorperazine edisylate oral solutions and injection, and prochlorperazine maleate tablets and extended-release capsules should be stored at a temperature less than 40 °C, preferably between 15 -30 °C; freezing of the oral solutions and injection should be avoided. Prochlorperazine suppositories should be stored at a temperature less than 37 °C. Prochlorperazine edisylate injection should be protected from light, which can cause discoloration; if discoloration occurs, the injection should be discarded.

Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

SRP: The scientific literature for the use of contact lenses by industrial workers is inconsistent. The benefits or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

This material is assumed to be combustible. As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.

As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.

Use safety glasses or goggles and protect exposed skin.

Engineering controls such as exhaust ventilation are recommended.

Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.

Chlorpromazine and some other antipsychotic drugs ... may block antihypertensive effects of guanethidine. /Phenothiazines/

Chlorpromazine is used concurrently with meperidine to enhance its analgesic effect. ... Prochlorperazine...reported to interact with meperidine.

Benztropine is useless in treating tardive dyskinesia caused by chlorpromazine & possibility exists that it contributes to this adverse effect. ... Other phenothiazines associated with tardive dyskinesia including ... prochlorperazine. Similarly acting phenothiazines would be expected to have capability of producing dyskinesia.

QT interval-prolonging medications, including cisapride, erythromycin, and quinidine /may produce/ additive QT interval prolongation increasing the risk of developing cardiac arrhythmias when /concurrently administered with phenothiazines/. /Phenothiazines/

For more Interactions (Complete) data for Prochlorperazine (30 total), please visit the HSDB record page.

Liver test abnormalities are uncommon during prochlorperazine therapy, perhaps because it is rarely given long term or in high doses chronically. Aminotransferase elevations can occur during therapy, but they are usually mild, asymptomatic and transient and reversible even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to prochlorperazine which resemble the cholestatic liver injury associated with chlorpromazine. The onset of jaundice is usually within 1 to 4 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed. Immunoallergic features (fever and eosinophilia) occur in some cases, but they are usually mild and self-limited; autoantibodies are rare. Liver biopsy typically shows a cholestatic hepatitis. Importantly, prochlorperazine jaundice can be prolonged and has been associated with rare cases of vanishing bile duct syndrome (Case 1) that can be fatal or ultimately require liver transplantation.

As a first-generation antipsychotic, prochlorperazine can cause a variety of adverse effects. Significant extrapyramidal symptoms, including acute dystonia, tardive dyskinesia, Parkinsonism, akathisia, and neuroleptic malignant syndrome. Anticholinergic side effects include anorexia, blurred vision, constipation, dry mucosa, and urinary retention. Antihistaminic side effects (blockage of H1 receptor) include sedation. Prochlorperazine can also lower the seizure threshold. It can also lead to prolonged QTc interval and cause other cardiac conduction abnormalities. Antiadrenergic effects (blockage of the alpha1-adrenergic receptor) can lead to orthostatic hypotension. Due to dopamine blockade in the tuberoinfundibular tract, hyperprolactinemia, amenorrhea, breast enlargement, and sexual dysfunction may also occur.

There are varying treatments available for extrapyramidal symptoms. Parkinsonism is treatable with benztropine or amantadine. Benztropine or diphenhydramine can treat acute dystonia. Akathisia is treatable with beta-blockers, benztropine, or benzodiazepines. Tardive dyskinesia is treatable by switching to atypical antipsychotics such as clozapine. Tetrabenazine is another option. For neuroleptic malignant syndrome, the healthcare provider should immediately discontinue prochlorperazine and give dantrolene (0.8 to 2.5 mg/kg given four times per day; up to 10 mg/day may be provided). Also, monitor white blood cell count and vitals, and cool and hydrate the patient as much as possible.

The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its antidopaminergic effects. Prochlorperazine blocks the D2 somatodendritic autoreceptor, resulting in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Prochlorperazine also has anti-emetic effects, which can be attributed to dopamine blockade in the chemoreceptor trigger zone. Prochlorperazine also blocks anticholinergic and alpha-adrenergic receptors, the blockade of alpha(1)-adrenergic receptors resulting in sedation, muscle relaxation, and hypotension.

/AQUATIC SPECIES/ Environmental fates and effects of pharmaceuticals in the aquatic environment have been the focus of recent research in environmental ecotoxicology. Worldwide studies of common over-the-counter pharmaceuticals have reported detectable levels in the aquatic environment, but there are few studies examining impacts on marine habitats. These drugs can affect the functions of various vertebrates and invertebrates. The stability of two pharmaceuticals, cyclizine (CYC) and prochlorperazine (PCZ), in seawater was examined under light and dark conditions, as well as the toxicity of these compounds to larvae of the barnacle Balanus amphitrite, which is a cosmopolitan marine organism found in most of the world's oceans. CYC was very stable under all the tested conditions. On the other hand, PCZ degraded in light but not in the dark, and was more stable in seawater than fresh water. For the barnacle larvae, the LC50 of prochlorperazine was 0.93 microg/mL and the LC50 for CYC was approximately 0.04 microg/mL.

Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus; LD₅₀=400mg/kg (orally in mice)

/SIGNS AND SYMPTOMS/ Symptoms of central nervous system depression to the point of somnolence or coma. Agitation and restlessness may also occur. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus.

/SIGNS AND SYMPTOMS/ Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

/SIGNS AND SYMPTOMS/ In general, overdosage of phenothiazines may be expected to produce effects that are extensions of common adverse reactions; severe extrapyramidal reactions, hypotension, and sedation have been the principal effects reported. CNS depression progressing to coma with areflexia or CNS stimulation with convulsions followed by respiratory depression may occur; patients with early or mild intoxication may experience drowsiness, restlessness, disorientation, confusion, and excitement. Other reported effects associated with acute phenothiazine overdosage have included shock (eg, ECG changes and cardiac arrhythmias), increased QT and PR intervals, non-specific ST and T wave changes, bradycardia, sinus tachycardia, bilateral bundle branch block, atrioventricular block, ventricular tachycardia, ventricular fibrillation, torsades de pointes, myocardial depression, agitation, dry skin, nasal congestion, urinary retention, oliguria, uremia, blurred vision, hypothermia, hyperthermia, mydriasis, miosis, tremor, muscle twitching, spasm or rigidity, seizures, muscular hypotonia, constipation, ileus, dry mouth, vomiting, difficulty in swallowing or breathing, cyanosis, and respiratory and/or vasomotor collapse, and pulmonary edema, possibly with sudden apnea. /Phenothiazine general Statement/

/SIGNS AND SYMPTOMS/ Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10 week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Prochlorperazine maleate is not approved for the treatment of patients with dementia-related psychosis

For more Human Toxicity Excerpts (Complete) data for Prochlorperazine (18 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

prochlorperazine

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Acute Exposure/ Phenothiazines (chlorpromazine, trifluoperazine, prochlorperazine, and fluphenazine) showed dose-dependent inhibition of phagocytosis of latex particles by cultured chick retinal pigment epithelial cells at concentrations of 10(-5)-10(-14) mol/L. Calmodulin antagonists (W-5, W-7, W-12, and W-13) showed similar effects as phenothiazines at concentrations of 10(-5)-10(-14) mol/L. These reactions were partially reversible at a concentration of 10(-9) mol/L. Cells cultured for 3 days in the presence of 10(-5) mol/L chlorpromazine or 10(-5) mol/L W-7 demonstrated morphologic alterations in their microvilli which were similar to those seen after cytochalasin B treatment, ie, thinning and elongation of the microvilli with honeycomb-like changes.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Pregnant Sprague-Dawley rats received 25 mg/kg of prochlorperazine, 20 mg/kg of fenfluramine, 75 mg/kg of propoxyphene or 200 mg/kg of diazepam daily between the 7th and 20th days of gestation. Vehicle control groups and a positive control group (vitamin A 40,000 IU/kg/day) were similarly prepared. Observations of reproductive performance were made and the offspring examined in a battery of neurobehavioral tests. Fenfluramine and prochlorperazine produced abnormalities in both the reproductive measures and neurobehavioral testing. Propoxyphene produced developmental delays and other signs of "pure" behavioral teratogenesis in that these effects were not anticipated in any of the observations of reproductive performance. Diazepam appeared to have the mildest effect on all the measurements taken.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Three psychotropic drugs were administered to pregnant rats and were then evaluated for their behavioral and reproductive effects in the offspring. Control rats received either saline or vitamin A. Prochlorperazine had the most disruptive effects on reproduction and growth, but had the least effect on behavior. Propoxyphene had no apparent effects on reproduction or growth, but produced a variety of behavioral changes. Fenfluramine was intermediate in its effects on reproduction and growth and had behavioral effects that were revealed in tests of preweaning development. ...

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents treated with certain antipsychotics.

/LABORATORY ANIMALS: Neurotoxicity/ While antiemetics do not induce peripheral neurotoxicity when administered systemically, it is not known whether peripheral nerve injury can occur as a result of inadvertent intraneural injection during intramuscular administration. The purpose of this study was to characterize the neurotoxic effect of three commonly used antiemetic agents (promethazine, dimenhydrinate, and prochlorperazine) as compared to saline in the rat sciatic nerve model. Intrafascicular and extrafascicular injection as well as direct application of the antiemetic drugs were performed. Nerves were harvested at 2 weeks postoperatively for histology and morphometry, with an additional sacrifice point at 8 weeks for the intrafascicular injection group. Injection injuries caused by antiemetic drugs differed depending on the agent injected and the location of injection. Extrafascicular injection and direct application caused no damage. Intrafascicular injection caused diffuse axonal injury in the promethazine and dimenhydrinate groups, while prochlorperazine caused only focal injury. Regeneration was prominent at 8 weeks in all intrafascicular injection groups in this rat model. Prochlorperazine thus appears to be less neurotoxic when injected intraneurally and should preferentially be used for intramuscular injections.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine edisylate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prochlorperazine edisylate/

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including prochlorperazine maleate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Prochlorperazine maleate/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Prochlorperazine dimaleate is included on this list. /Prochlorperazine dimaleate/

For more FDA Requirements (Complete) data for Prochlorperazine (9 total), please visit the HSDB record page.

N - Nervous system

QN - Nervous system

Prochlorperazine is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons. It also exerts its anti-emetic actions via anti-dopaminergic effects, where it displays similar efficacy as ondansteron, a 5HT-3 receptor antagonist and anti-emetic, in preventing delayed nausea and vomiting. Prochlorperazine was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors. The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well. Compared to other phenothiazine derivatives, prochlorperazine is less sedating and has a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics. Other than its primary action on D2 receptors, one study showed that prochlorperazine may inhibit the P2X7 receptor in human macrophages, leading to inhibition of calcium ion influx.

The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its anti-dopaminergic effects. Prochlorperazine blocks the D2 dopamine receptors in the brain, which are somatodendritic autoreceptors. Inhibition of D2 receptor signaling results in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Nausea and vomiting are proposed to arise from peripheral or central stimulation of serotonin type 3 (5-HT3) and dopamine type 2 receptors, the predominant receptors expressed at the chemoreceptor trigger zone (CTZ). Prochlorperazine exerts antiemetic effects and was shown to inhibit apomorphine-induced vomiting by blocking D2 dopamine receptors in the CTZ..

The principal pharmacologic effects of prochlorperazine are similar to those of chlorpromazine. Prochlorperazine has weak anticholinergic effects, moderate sedative effects, and strong extrapyramidal effects. Prochlorperazine has strong antiemetic activity.

The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/

In the CNS, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, and hypothalamus. Phenothiazines generally do not produce substantial cortical depression; however, there is minimal information on the specific effects of phenothiazines at the cortical level. Phenothiazines also act in the basal ganglia, exhibiting extrapyramidal effects. The precise mechanism(s) of action, including antipsychotic action, of phenothiazines has not been determined, but may be principally related to antidopaminergic effects of the drugs. There is evidence to indicate that phenothiazines antagonize dopamine-mediated neurotransmission at the synapses. There is also some evidence that phenothiazines may block postsynaptic dopamine receptor sites. However, it has not been determined whether the antipsychotic effect of the drugs is causally related to their antidopaminergic effects. Phenothiazines also have peripheral and/or central antagonistic activity against alpha-adrenergic, serotonergic, histaminic (H1-receptors), and muscarinic receptors. Phenothiazines also have some adrenergic activity, since they block the reuptake of monoamines at the presynaptic neuronal membrane, which tends to enhance neurotransmission. The effects of phenothiazines on the autonomic nervous system are complex and unpredictable because the drugs exhibit varying degrees of alpha-adrenergic blocking, muscarinic blocking, and adrenergic activity. The antipsychotic activity of phenothiazines may be related to any or all of these effects, but it has been suggested that the drugs' effects on dopamine are probably most important. It has also been suggested that effects of phenothiazines on other amines (eg, gamma-aminobutyric acid [GABA]) or peptides (eg, substance P, endorphins) may contribute to their antipsychotic effect. Further study is needed to determine the role of central neuronal receptor antagonism and of effects on biochemical mediators in the antipsychotic action of the phenothiazines and other antipsychotic agents. /Phenothiazine General Statement/

Although the exact mechanism(s) of action has not been conclusively determined, phenothiazines have an antiemetic effect. The antiemetic activity may be mediated via a direct effect of the drugs on the medullary chemoreceptor trigger zone (CTZ), apparently by blocking dopamine receptors in the CTZ. Phenothiazines inhibit the central and peripheral effects of apomorphine and ergot alkaloids. Phenothiazines generally do not inhibit emesis caused by the action of drugs at the nodose ganglion or by local action on the GI tract. /Phenothiazine General Statement/

For more Mechanism of Action (Complete) data for Prochlorperazine (15 total), please visit the HSDB record page.

Prochlorperazine undergoes hepatic metabolism involving oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid. The oxidation reaction is mediated by CYP2D6. N-desmethyl prochlorperazine was detected in the plasma, as well as prochlorperazine sulfoxide, prochlorperazine 7-hydroxide and prochlorperazine sulfoxide 4'-N-oxide, following oral and buccal administration. Prochlorperazine may enter the enterohepatic circulation.

Most metabolites of phenothiazines are pharmacologically inactive; however, certain metabolites (eg, 7-hydroxychlorpromazine, mesoridazine) show moderate pharmacologic activity and may contribute to the action of the drugs. There is limited evidence to indicate that some phenothiazines (eg, chlorpromazine) may induce their own metabolism. /Phenothiazine General Statement/

Metabolized primarily in liver /by/ oxidation, hydroxylation, demethylation, sulfoxide formation and conjugation with glucuronic acid; metabolic alterations in side chain may also occur.

After chronic administration of piperazine-substituted phenothiazine drugs ... to rats, tissues contained drug metabolites, in which piperazine ring fission by multiple oxidative n-dealkylation had occurred to give substituted ethylenediamine. Thus, n-[gamma-(2-chlorphenothiazinyl-10)-propyl]ethylenediamine ... from prochlorperazine ...

Yields 2-chloro-10-(3-(4-methylpiperazin-1-yl)propyl)phenothiazine-n-oxide and 2-chloro-10-(3-(4-methylpiperazin-1-yl)propyl)phenothiazine sulfoxide in rats

For more Metabolism/Metabolites (Complete) data for Prochlorperazine (7 total), please visit the HSDB record page.

YHP6YLT61T

PROCHLORPERAZINE

Established Pharmacologic Class [EPC] - Phenothiazine

Chemical Structure [CS] - Phenothiazines

Prochlorperazine is a Phenothiazine.

PROCHLORPERAZINE

Drugs used to prevent NAUSEA or VOMITING.

Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Following oral administration, prochlorperazine is reported to be well absorbed from the gastrointestinal tract. The onset of pharmacological action is about 30 to 40 minutes following oral administration and 10 to 20 minutes following intramuscular administration. The duration of action for all routes is about 3 to 4 hours. Following oral administration in healthy volunteers, the mean oral bioavailability was about 12.5%. In these patients, the time to reach the peak plasma concentrations was about 5 hours. Repeated oral dosing resulted in an accumulation of prochlorperazine and its metabolite. Following multiple twice daily dosing, the steady state of prochlorperazine was reached by 7 days.

Prochlorperazine is reported to be mainly excreted via the feces and bile. Low quantities of unchanged prochlorperazine and its metabolite were detectable in the urine.

In a preliminary pharmacokinetic study involving healthy volunteers, the mean apparent volume of distribution following intravenous administration of 6.25 mg and 12.5 mg prochlorperazine were approximately 1401 L and 1548 L, respectively. Prochlorperazine is reported to be distributed to most body tissues with high concentrations being distributed into liver and spleen. There is evidence that phenothiazines are excreted in the breast milk of nursing mothers.

The mean plasma clearance (CL) of prochlorperazine following intravenous administration in healthy volunteers was approximately 0.98L/h x kg. The mean renal clearance was about 23.6 mL/h.

Phenothiazines are generally well absorbed from the GI tract and from parenteral sites; however, absorption may be erratic, particularly following oral administration. Considerable interindividual variations in peak plasma concentrations have been reported. The variability may result from genetic differences in the rate of metabolism, biodegradation of the drug in the GI lumen, and/or metabolism of the drug during absorption (in the GI mucosa) and first pass through the liver.

Phenothiazines are highly bound to plasma proteins.

Among the most commonly used "general purpose" antinauseants and antiemetics

THERAPEUTIC CATEGORY: Antiemetic; antipsychotic. In treatment of vertigo

THERAPEUTIC CATEGORY (VETERINARY): Antiemetic

Use (kg) in USA (2002): 584

For the symptomatic management of psychotic disorders, short term management of nonpsychotic anxiety in patients with generalized anxiety disorder, and for the control of severe nausea and vomiting of various causes.

Preparation: R.J. Horclois, British patent 780193; French patent 1167627; US patent 2902484 (1957, 1958, 1959, all to Rhone-Poulenc).

A toluene solution of 1-(3-chloropropyl)-4-methylpiperazine and 2-chlorophenothiazine is refluxed with sodamide for several hours. After filtering and distilling of the toluene, the prochlorperazine is obtained by short-path distillation under high vacuum.

Prochlorperazine preparations: (AHFS, 2010)

Prochlorperazine Edisylate preparations: (AHFS, 2010)

Prochlorperazine Maleate preparations: (AHFS, 2010)

Compazine /is the/ trademark for a brand of prochlorperazine, as the maleate or the edisylate

Prochlorperazine has questionable utility as an antipsychotic agent... it is rarely employed in psychiatry