Chlorpromazine Chemical Properties

Melting point:

56.5°C

Boiling point:

bp0.8 200-205°

Density 

1.1644 (rough estimate)

refractive index 

1.6230 (estimate)

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

pKa 9.3(H2O,t =24±1) (Uncertain)

form 

Solid

color 

White to Off-White

NIST Chemistry Reference

Chlorpromazine(50-53-3)

EPA Substance Registry System

Chlorpromazine (50-53-3)

Safety Information

Hazardous Substances Data

50-53-3(Hazardous Substances Data)

Toxicity

LD50 oral in rat: 142mg/kg

Chlorpromazine Usage And Synthesis

Description

This phenothiazine with sedative properties is used in human medicines and has induced contact dermatitis in nurses or in those working in the pharmaceutical industry. It is also used in veterinary medicine to avoid mortality of pigs during transportation. It is a sensitizer and a photosensitizer.

Chemical Properties

Oily liquid; amine odor.

Uses

antiemetic, antipsychotic

Uses

In psychiatric practice, chlorpromazine is used in various conditions of psychomotor excitement in patients with schizophrenia, chronic paranoid and also manic-depressive conditions, neurosis, alcohol psychosis and neurosis accompanied by excitement, fear, stress, and insomnia. In comparison with other neuroleptics, chlorpromazine is unique in that it has an expressed sedative effect. It is sometimes used in anesthesiological practice for potentiating narcosis. It also has moderate anticonvulsant action.

Uses

Chlorpromazine is approved by FDA for use in humans for the management of psychotic disorders (i.e., control of mania, treatment of schizophrenia); control of nausea and vomiting; relief of apprehension before surgery; acute intermittent porphyria; adjunctive treatment of tetanus; intractable hiccups; combativeness or explosive hyperexcitable behavior in children aged 1–12 years; and short-term treatment of hyperactivity in children with symptoms of impulsivity, difficulty sustaining attention, aggressiveness, mood lability, and poor frustration tolerance. Chlorpromazine is commonly used off-label for treatment of behavioral symptoms associated with dementia in the elderly and psychosis and agitation related to Alzheimer’s dementia; however, it carries a boxed warning regarding increased risk of death in patients with dementia-related psychosis. Chlorpromazine is also used off-label for managing agitation in terminal cancer patients, autonomic dysreflexia, cancer pain, adjunctive treatment of cholera, migraine headaches, opioid withdrawal, ocular pain, paralytic ileus, and phantom limb syndrome.
In veterinary medicine, the use of chlorpromazine has been largely replaced by the phenothiazine acepromazine due to its more favorable pharmacokinetic profile. Chlorpromazine may be used as an antiemetic for small animals or for preoperative sedation. Chlorpromazine may also be used for management of hypertension in dogs and cats.

Definition

ChEBI: A substituted phenothiazine in which the ring nitrogen at position 10 is attached to C-3 of an N,N-dimethylpropanamine moiety.

brand name

Thorazine (GlaxoSmithKline).

Hazard

Toxic by ingestion.

Contact allergens

This phenothiazine with sedative properties is used in human medicine and induced contact dermatitis in nurses or those working in the pharmaceutical industry. It is also used in veterinary medicine to avoid mortality of pigs during transportation. It is a sensitizer and a photosensitizer.

Synthesis

Chlorpromazine, 2-chloro-10-(3-dimethylaminopropyl)phenothiazine, is synthesized in an analogous manner, except by alkylation of 2-chlorophenothiazine with 3-dimethylaminopropylchloride.

Environmental Fate

Acute and chronic toxicity due to chlorpromazine generally manifests as an extension of normal pharmacological activity. The precise mechanism of action of chlorpromazine, and other phenothiazines, is unknown; however, it is thought to primarily involve antagonism of dopaminergic (D2) neurotransmission at synaptic sites and blockade of postsynaptic dopamine receptor sites at the subcortical levels of the reticular formation, limbic system, and hypothalamus. This activity contributes to chlorpromazine’s extrapyramidal reactions. Chlorpromazine also has strong central and peripheral activity directed against adrenergic receptors and weak activity against serotonergic, histaminic (H1), and muscarinic receptors. Chlorpromazine has slight ganglionic blocking action. Chlorpromazine is known to depress vasomotor reflexes medicated by the hypothalamus and/or brain stem; inhibit release of growth hormone; antagonize secretion of prolactin release-inhibiting hormone; and reduce secretion of corticotropin-regulatory hormone.
Chlorpromazine also has direct effects on cardiac myocytes; it can induce early after-depolarizations, block depolarizing sodium channels, and cause significant prolongation of the QTc interval.
Chlorpromazine may be irritating to eyes, mucous membranes, and skin. Contact and inhalation should be avoided.

Metabolic pathway

The in vivo photodegradation of chlorpromazine in rat skin exposed to UV-A results in the formation of promazine and 2-hydroxypromazine in irradiated rats, but not in the skin of rats kept in the dark. Chlorpromazine sulfoxide is a major metabolite of chlorpromazine, found in smaller quantity in the skin of irradiated rats compared with those kept in the dark. Chlorpromazine sulfoxide is not a photoproduct of chlorpromazine under the experimental conditions.

Toxicity evaluation

Chlorpromazine exists as both a vapor and particulate at ambient atmospheric conditions. Chlorpromazine vapor is degraded by photochemically produced hydroxyl radicals with an estimated half-life of 1.6 h. Chlorpromazine particulate is removed by wet or dry deposition. Chlorpromazine is likely to be immobile in soil (Koc 9900, pKa 9.3) and to adsorb to sediment if released into water. It is not expected to volatilize from soil or water. There is high potential for bioconcentration.

Chlorpromazine(50-53-3)Related Product Information

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• ChlorproMazine Sulfoxide
• Chlorpromazine hydrochloride
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• PERPHENAZINE
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