Chlorpromazine hydrochloride Chemical Properties

Melting point:

192-196°C

Density 

1.2221 (estimate)

Flash point:

9℃

storage temp. 

2-8°C

solubility 

Very soluble in water, freely soluble in ethanol (96 per cent). It decomposes on exposure to air and light.

form 

Powder/Solution

color 

White to off-white or clear colorless

PH

pH (50g/L, 25℃) : 4.0～5.0

Water Solubility 

>=10 g/100 mL at 24 ºC

Merck 

14,2185

BRN 

3779989

BCS Class

3

Stability:

Stable. Combustible. Incompatible with strong oxidizing agents. Air and light sesnsitive.

CAS DataBase Reference

69-09-0(CAS DataBase Reference)

EPA Substance Registry System

Chlorpromazine hydrochloride (69-09-0)

Safety Information

Hazard Codes 

T+,T,F

Risk Statements 

25-26-39/23/24/25-23/24/25-11

Safety Statements 

28-36/37-45-16

RIDADR 

UN 2811 6.1/PG 1

WGK Germany 

3

RTECS 

SO1750000

F 

3-10-21

TSCA 

Yes

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

29173980

Toxicity

LD50 orally in rats: 225 mg/kg (Goldenthal)

MSDS

• Language:English Provider:Largactil
• Language:English Provider:SigmaAldrich

Chlorpromazine hydrochloride Usage And Synthesis

Chemical Properties

Crystalline Solid

Originator

Thorazine, SKF, US ,1954

Uses

Chlorpromazine hydrochloride is used in the treatment of schizophrenia; anti-emetic; as an antipsychotic in pills, injections, and suppositories; to relieve nausea and vomiting associated with malignant diseases. In veterinary medicine, it is used as an anti-emetic, tranquilizer and sedative. It has slight antihistaminic and anti adrenaline actions. It is a peripheral vasodilator and adepressant that blocks dopamine receptors in the central nervous system.

Uses

Used as an Antiemetic, Antipsychotic

Uses

Antiemetic;Dopamine antagonist

Definition

ChEBI: The hydrochloride salt of chlorpromazine.

Manufacturing Process

To a boiling suspension of 11.6 g of chlorophenothiazine (consisting of a mixture of two isomers melting at 196° to 198°C and 116° to 117°C, respectively, the latter in minor proportion) and 2.4 g of sodium amide (80%) in 60 cc of xylene, there are added over a period of one hour 7.5 g of 3-
dimethylamino-1-chloropropane in solution in its own weight of xylene. At the end of the addition, heating is continued for one hour under reflux. After cooling, the contents are taken up in acidified water and the xylene separated. The aqueous layer is made strongly alkaline by means of sodium hydroxide in order to liberate the base and this is extracted with ether. On distillation of the ethereal extract there is obtained 10-(3'-dimethylamino-propyl)- chlorophenothiazine which distills at 200° to 205°C under a pressure of 0.8 mm Hg. Its hydrochloride, recrystallized from chlorobenzene, melts at 177° to 178°C. The chlorophenothiazine may be prepared by reacting mchlorodiphenylamine with sulfur in the presence of an iodine catalyst.

brand name

Thorazine (GlaxoSmithKline).

Therapeutic Function

Tranquilizer

General Description

Chlorpromazinehydrochloride, 2-chloro-10-[3-(dimethylamino)propyl]phenothiazine monohydrochloride (Thorazine), was the first phenothiazinecompound introduced into therapy. It is still usefulas an antipsychotic. Other uses are in nausea, vomiting, andhiccough. Oral doses of chlorpromazine and thioridazinehave systemic availability of 25% to 35% because of significantfirst-pass metabolism. Chlorpromazine and other phenothiazinesare metabolized extensively by CYP2D6. In contrast, bioavailability of chlorpromazine may beincreased up to 10-fold with injections, but the clinical doseusually is decreased by only threefold to fourfold.Chlorpromazine may weakly induce its own hepatic metabolism,because its concentration in blood is lower after severalweeks of treatment at the same dosage. Alterations of GImotility also may contribute. The drug has significant sedativeand hypotensive properties, possibly reflecting centralhistaminergic and peripheral α₁-noradrenergic blockingactivity, respectively. Effects of peripheral anticholinergic activityare common. As with the other phenothiazines, the effectsof other CNS-depressant drugs, such as sedatives andanesthetics, can be potentiated.

General Description

White or creamy-white odorless crystalline powder with very bitter taste. pH (5% aqueous solution) 4.0-5.5. pH (10% aqueous solution) 4-5.

Air & Water Reactions

Decomposes on exposure to air and light. becoming yellow, pink and, finally, violet. Water soluble.

Reactivity Profile

Chlorpromazine hydrochloride is incompatible in aqueous solution with sodium salts of barbiturates and other alkaline solutions. Solutions may be stabilized by addition of antioxidants and storing under nitrogen.

Fire Hazard

Flash point data for Chlorpromazine hydrochloride are not available; however, Chlorpromazine hydrochloride is probably combustible.

Biological Activity

dopamine receptors are a class of g protein-coupled receptors that are prominent in the central nervous system. dopamine receptors are implicated in many neurological processes. thus, dopamine receptors are common neurologic drug targets. antipsychotics are often dopamine receptor antagonists while typically psychostimulants are indirect agonists of dopamine receptors. chlorpromazine is a dopamine antagonist.

Biochem/physiol Actions

Chlorpromazine demonstrates cytotoxic and antiproliferative activity against leukemic cells, but does not affect the viability of normal lymphocytes.

Safety Profile

Poison by ingestion, intraperitoneal, intravenous, and subcutaneous routes. An experimentalteratogen. Experimental reproductive effects. An anti-emetic and antipsychotic drug. Human systemic effects: anorexia (human), excitement, gastrointestinal changes, irritability, pulse rate increase, respiratory stimulation, rigidity, somnolence, sweating. Mutation data reported. When heated to decomposition it emits very toxic fumes of Cl-, NOx, and SOx.

Veterinary Drugs and Treatments

The clinical use of chlorpromazine as a neuroleptic agent has diminished, but the drug is still used for its antiemetic effects in small animals and occasionally as a preoperative medication and tranquilizer. As an antiemetic, chlorpromazine will inhibit apomorphineinduced emesis in the dog but not the cat. It will also inhibit the emetic effects of morphine in the dog. It does not inhibit emesis caused by copper sulfate, or digitalis glycosides.
Once the principle phenothiazine used in veterinary medicine, chlorpromazine has been largely supplanted by acepromazine. It has similar pharmacologic activities as acepromazine, but is less potent and has a longer duration of action. For further information, refer to the acepromazine monograph.

in vitro

the antipsychotic activity of chlorpromazine has been associated with its ability to act as a dopamine-receptor antagonist. the manner in which chlorpromazine, with its phenothiazine ring structure, interacted with a receptor for dopamine. furthermore, chlorpromazine inhibited the binding of [3h]spiperone, and the inhibition curve was consistent with a single class of binding sites [1].

in vivo

daily administration of chlorpromazine to rats for 21 days induced catalepsy, tolerance to catalepsy and locomotor sensitization following pcp challenge. results suggest that daily chlorpromazine treatment induced da/nmda-receptor sensitization to total locomotor activity following pcp challenge [2].

Drug interactions

Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone.
Anti-arrhythmics: increased risk of ventricular arrhythmias with anti-arrhythmics that prolong the QT interval and disopyramide; avoid with amiodarone and dronedarone.
Antibacterials: increased risk of ventricular arrhythmias with delamanid, moxifloxacin and telithromycin - avoid with moxifloxacin.
Antidepressants: increased level of tricyclics, possibly increased risk of ventricular arrhythmias and antimuscarinic side effects; increased risk of ventricular arrhythmias with citalopram and escitalopram - avoid; increased risk of convulsions with vortioxetine.
Anticonvulsants: antagonises anticonvulsant effect; concentration of fosphenytoin and phenytoin possibly increased or decreased; concentration of both drugs reduced with phenobarbital.
Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol.
Antipsychotics: increased risk of ventricular arrhythmias with droperidol and pimozide - avoid; concentration of haloperidol possibly increased; possible increased risk of ventricular arrhythmias with risperidone.
Antivirals: concentration possibly increased with ritonavir; increased risk of ventricular arrhythmias with saquinavir - avoid.
Anxiolytics and hypnotics: increased sedative effects.
Atomoxetine: increased risk of ventricular arrhythmias.Beta-blockers: enhanced hypotensive effect; concentration of both drugs may increase with propranolol; increased risk of ventricular arrhythmias with sotalol.
Cytotoxics: increased risk of ventricular arrhythmias with vandetanib - avoid; increased risk of ventricular arrhythmias with arsenic trioxide.
Diuretics: enhanced hypotensive effect.
Lithium: increased risk of extrapyramidal side effects and possibly neurotoxicity.
Pentamidine: increased risk of ventricular arrhythmias.
Ulcer-healing drugs: effects enhanced by cimetidine.

Metabolism

Chlorpromazine is subject to considerable first-pass metabolism in the gut wall and is also extensively metabolised in the liver. Paths of metabolism of chlorpromazine include hydroxylation and conjugation with glucuronic acid, N-oxidation, oxidation of a sulfur atom, and dealkylation.
Chlorpromazine is excreted in the urine and bile in the form of both active and inactive metabolites; there is some evidence of enterohepatic recycling.

References

[1] harrold mw, chang ya, wallace ra, farooqui t, wallace lj, uretsky n, miller dd. charged analogues of chlorpromazine as dopamine antagonists. j med chem. 1987 sep;30(9):1631-5.
[2] nsimba se. effects of daily chlorpromazine administration on behavioural and physiological parameters in the rat. indian j physiol pharmacol. 2009 jul-sep;53(3):209-18.

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