Chlorprothixene

315.86

315.86

204-032-8

DTXSID4022810

Pale yellow crystals.

N - Nervous system

2932999099

28.5

5.2

1.1048 (rough estimate)

97-98 °C

160 °C @ Press: 0.04 Torr

216.9±28.7 °C

1.6000 (estimate)

14 [ug/mL]

-20°C

9.06E-08mmHg at 25°C

LD50 oral in rabbit: 182mg/kg

SLIGHT AMINE-LIKE ODOR

Incompatible with acids, alkalies, phenobarbital, thiopental sodium, mepazine.

Ⅲ

2811

6.1

SENSITIVE TO LIGHT & AIR

P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501

H301

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 5 companies from 1 notifications to the ECHA C&L Inventory.

Concurrent use with alcohol or CNS depression-producing medications, anesthetics, barbiturates, and opioid (narcotic) analgesics may potentiate and prolong the CNS depressant effects of either these medications or the thioxanthenes; dosage adjustments may be necessary. /Thioxanthenes/|Concurrent use with thioxanthenes may inhibit the CNS-stimulating effects of amphetamines due to alpha-adrenergic blockage by the thioxanthenes; also, the antipsychotic effects of thioxanthenes may be reduced when they are used concurrently with amphetamines. /Thioxanthenes/|Concurrent use of antacids or adsorbent antidiarrheals may inhibit the absorption of an orally administered thioxanthene. /Thioxanthenes/|Anticholinergic effects, especially confusion, hallucinations, nightmares, and increased intraocular pressure, may be potentiated when anticholinergics or other medications with anticholinergic action, antidyskinetic agents, or antihistamines are used concurrently with thioxanthenes, because of secondary anticholinergic action of thioxanthenes. /Thioxanthenes/|For more Interactions (Complete) data for CHLORPROTHIXENE (18 total), please visit the HSDB record page.

LD50 Rat oral 380 mg/kg

Antipsychotic Agents; Dopamine Antagonists|IT MAY BE OF VALUE IN THE SYMPTOMATIC TREATMENT OF AGITATED STATES ASSOCIATED WITH NEUROSES, DEPRESSION OR SCHIZOPHRENIA. DRUG APPEARS TO BE MORE EFFECTIVE IN THE MANAGEMENT OF ACUTE SCHIZOPHRENIA THAN OF CHRONIC SCHIZOPHRENIA.|...IT HAS BEEN USED IN THE TREATMENT OF...PSYCHOTIC & SEVERE NEUROTIC CONDITIONS IN WHICH ANXIETY, AGITATION, AND TENSION PREDOMINATE.|.../IT/ MAY BE USED TO POTENTIATE CENTRAL NERVOUS SYSTEM DEPRESSANTS & CONCOMITANTLY WITH ANTICONVULSANTS &/OR ELECTROSHOCK TREATMENT.|Indicated for management of primary and secondary symptoms of psychotic disorders. /Thioxanthenes; Included in US product labeling/

CHLORPROTHIXENE IS CONTRAINDICATED IN PATIENTS WHO ARE HYPERSENSITIVE TO THE DRUG; THE POSSIBILITY OF CROSS-SENSITIVITY TO PHENOTHIAZINES & TO THIOTHIXENE MUST BE BORNE IN MIND.|CHLORPROTHIXENE IS CONTRAINDICATED IN PATIENTS WITH CIRCULATORY COLLAPSE & IN THOSE WITH CONGESTIVE FAILURE, CARDIAC DECOMPENSATION, CORONARY ARTERY, OR CEREBRAL VASCULAR DISORDERS.|CHLORPROTHIXENE IS CONTRAINDICATED IN COMATOSE STATES, PARTICULARLY THOSE INDUCED BY CNS DEPRESSANT DRUGS.|WHEN CHLORPROTHIXENE IS USED CONCOMITANTLY WITH OTHER CNS DEPRESSANTS, CAUTION MUST BE OBSERVED TO AVOID OVERDOSAGE...|For more Drug Warnings (Complete) data for CHLORPROTHIXENE (27 total), please visit the HSDB record page.

4(?). 4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 50-500 MG/KG; BETWEEN 1 TEASPOON AND 1 OUNCE FOR 70 KG PERSON (150 LB).

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. (See all compounds classified as Antipsychotic Agents.)|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. (See all compounds classified as Dopamine Antagonists.)

.../IT/ IS PARTIALLY ABSORBED FROM THE GI TRACT. FOLLOWING IM ADMIN, THE DRUG EXERTS ITS EFFECTS WITHIN 10-30 MINUTES. IT IS METABOLIZED, PRESUMABLY IN THE LIVER...FREE CHLORPROTHIXENE & ITS SULFOXIDE METABOLITE ARE EXCRETED IN THE URINE & FECES.|TRICYCLIC AGENT, CHLORPROTHIXENE, IS...EXTENSIVELY DISTRIBUTED IN BODY & HAS OVERALL DISTRIBUTION VOL IN MAN APPROACHING 1000 L...|AFTER IV ADMIN PHARMACOKINETICS FOLLOWED 2 COMPARTMENT MODEL. ...TOTAL VOL OF DISTRIBUTION WAS VERY LARGE. AFTER ORAL ADMIN (15 MG) BIOAVAILABILITY WAS POOR, ALTHOUGH ABSORPTION OF CMPD FROM THE GUT APPEARED TO BE GOOD.|METABOLISM OCCURRED MORE RAPIDLY WITH INCR AGE FROM 3-24 WK IN RATS. LEVELS OF CHLORPROTHIXENE, N-DEMETHYLCHLORPROTHIXENE & TOTAL AMINES IN BRAIN, LIVER, KIDNEYS & LUNG OF 3-WK OLD RATS WERE ABOUT TWICE THOSE IN 6-WK OLD RATS. AMT IN ORGANS WERE HIGHER IN FEMALES THAN IN MALES.|After 1 hour intravenous chlorprothixene infusion, the maximum serum concentration of chlorprothixene was 430 ng/ml, which subsequently decreased with a terminal elimination half-life of 25.8 hours. The total serum clearance and the apparent volume of distribution at steady state were 867 ml/min and 1035 l, respectively. ... Chlorprothixene bioavailability relative to the oral soution was 56.45 with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameterws showed wide inter-subject varioations.

UNCHANGED CHLORPROTHIXENE, THE SULFOXIDE DERIVATIVE & N-DEMETHYL SULFOXIDE HAVE BEEN IDENTIFIED IN THE URINE OF TREATED DOGS & RATS. HYDROXYLATION & GLUCURONIDATION ALSO OCCUR IN DOGS, BUT IDENTIFICATION OF THOSE BIOTRANSFORMATION PRODUCTS HAS NOT BEEN ACCOMPLISHED.|YIELDS DEMETHYLCHLORPROTHIXENE IN RAT. /FROM TABLE/|FOLLOWING ORAL ADMIN TO DOG & PSYCHIATRIC PT SEVERAL 3-, 7-, 4-, 6-, & 8-HYDROXYLATED METABOLITES FOUND IN URINE & FECES. HYDROXYLATION WAS FOLLOWED BY CONJUGATION WITH GLUCURONIC &/OR SULFURIC ACID FOR EXCRETION.|DRUG ADMIN TO RATS BY GAVAGE AT 100 MG/KG WAS METABOLIZED MORE RAPIDLY WITH INCR AGE FROM 3-24 WK.

AFTER IV ADMIN PHARMACOKINETICS FOLLOWED 2 COMPARTMENT MODEL. T/2 IN SECOND PHASE OF ELIMINATION WAS 5-12 HR...|TRICYCLIC AGENT, CHLORPROTHIXENE, ...HAS...BIOLOGICAL T/2 OF 8-12 HR.

...IT CAN BE EXPECTED TO DEPRESS THE CNS AT THE SUBCORTICAL LEVEL OF THE BRAIN, THE MIDBRAIN, & THE BRAIN STEM RETICULAR FORMATION.|.../IT/ IS MORE ACTIVE THAN CHLORPROMAZINE IN INHIBITING POSTURAL REFLEXES & MOTOR COORDINATION & LESS ACTIVE IN ANTIHISTAMINIC EFFECTS. CHLORPROTHIXENE POSSESSES SEDATIVE, ADRENOLYTIC, HYPOTHERMIC, ANTICHOLINERGIC, & ANTIEMETIC PROPERTIES.|Thioxanthenes are thought to benefit psychotic conditions by blocking postsynaptic dopamine receptors in the brain. They also produce an alpha-adrenergic blocking effect and depress the release of most hypothalamic and hypophyseal hormones. However, the concentration of prolactin is increased due to blockade of prolactin inhibitory factor (PIF), which inhibits the release of prolactin from the pituitary gland. /Thioxanthenes/|Chlorprothixene also inhibits the medullary chemoreceptor trigger zone to produce an antiemetic effect, and is also thought to cause an indirect reduction of stimuli to the brain stem reticular system to produce a sedative effect.

Treatment is essentially symptomatic and supportive and may consist of the following: to decrease absorption - early gastric lavage is often helpful. Not attempting to induce emesis because a dystonic reaction of the head and neck may develop that could result in aspiration of vomitus. Administering activated charcoal slurry. Administering saline cathartic. /Thioxanthenes/|Specific treatment: controlling cardiac arrhythmias with iv phenytoin, 9 to 11 mg/kg of body weight. Digitalizing for cardiac failure. Administering a vasopressor, such as norepinephrine or phenylephrine, for hypotension (not using epinephrine, which may cause paradoxical hypotension). Controlling convulsions with diazepam followed by phenytoin, 15 mg/kg, administered at a rate no faster than 50 mg/min. Benztropine or diphenhydramine may be administered to manage acute parkinsonian symptoms. Severe CNS depression may require administration of a stimulant such as amphetamine or dextroamphetamine (picrotoxin or pentylenetetrazol should be avoided as it may induce convulsions). Monitoring: monitoring cardiovascular function (for not less than 5 days). Supportive care: maintaining respiratory function and body temperature. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation. Note: Dialysis of thioxanthenes has not been successful. /Thioxanthenes/

NO HUMAN FATALITIES FROM OVERDOSES ARE KNOWN. COMPLETE RECOVERY WITHOUT SEQUELAE HAS OCCURRED FOLLOWING SINGLE DOSES UP TO 1075 MG IN CHILDREN & 8 G IN ADULTS.|Clinical effects of overdose include convulsions; severe difficulty in breathing; severe drowsiness or coma; fast heartbeat; fever; hypotension (severe dizziness); severe muscle trembling, jerking, stiffness, or uncontrolled movements; small pupils; unusual excitement; and unusual severe tiredness or weakness. /Thioxanthenes/|TWO CASE REPORTS DESCRIBING THE OCCURRENCE OF VOMITING IN 2 PATIENTS 9-YR OLD ABRUPTLY WITHDRAWN FROM DRUG.|Ophthalmologic examinations may be required at periodic intervals during high-dose or prolonged therapy since deposition of particulate matter in the lens and cornea has occurred. /Thioxanthenes/|The leukopenic and thrombocytopenic effects of thioxanthenes may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. /Thioxanthenes/

Chlorprothixene

INCOMPATIBILITIES: INCOMPATIBLE WITH ACIDS, ALKALIES, PHENOBARBITAL, THIOPENTAL SODIUM, MEPAZINE.

THIN-LAYER CHROMATOGRAPHY OF BASIC DRUGS ON SILICA GEL G.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals