69-09-0 Usage
Chemical Properties
Crystalline Solid
Originator
Thorazine, SKF, US ,1954
Uses
Different sources of media describe the Uses of 69-09-0 differently. You can refer to the following data:
1. 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.
2. Antiemetic;Dopamine antagonist
3. Used as an Antiemetic, Antipsychotic
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.
Therapeutic Function
Tranquilizer
General Description
Different sources of media describe the General Description of 69-09-0 differently. You can refer to the following data:
1. 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.
2. 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.
Clinical Use
#N/A
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.
Check Digit Verification of cas no
The CAS Registry Mumber 69-09-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 9 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 69-09:
(4*6)+(3*9)+(2*0)+(1*9)=60
60 % 10 = 0
So 69-09-0 is a valid CAS Registry Number.
InChI:InChI=1/C17H19ClN2S.ClH/c1-19(2)10-5-11-20-14-6-3-4-7-16(14)21-17-9-8-13(18)12-15(17)20;/h3-4,6-9,12H,5,10-11H2,1-2H3;1H
69-09-0Relevant articles and documents
Preparation method of chlorpromazine hydrochloride
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Paragraph 0018; 0025-0051, (2021/09/26)
The invention relates to a preparation method of chlorpromazine hydrochloride, and belongs to the technical field of medicine preparation. According to the method, 2-chlorophenothiazine and N, N-dimethyl-3-chloropropylamine are used as raw materials, an N-methyl pyrrolidone organic solvent is adopted, chlorpromazine is generated under the action of a 4-dimethylaminopyridine catalyst, the obtained chlorpromazine and hydrogen chloride gas are salified, and chlorpromazine hydrochloride is obtained. According to the method, a toxic toluene reagent is not needed, and an N-methyl pyrrolidone organic solvent is adopted, so that the method is more environment-friendly, and is more beneficial to recovery of chlorpromazine, and the yield and purity of chlorpromazine are improved. A large amount of sodium hydroxide does not need to be added, sodium hydroxide and tetrabutylammonium bromide in an original process can be replaced by selecting 4-dimethylaminopyridine, and the yield and purity of chlorpromazine hydrochloride are remarkably improved. By controlling the conditions of the salt forming reaction of hydrochloric acid, the crystallization and purification of chlorpromazine hydrochloride are facilitated, and high-purity chlorpromazine hydrochloride can be obtained.
