クロルプロチキセン

169.8 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated]

168.45 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Chlorprothixene blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis.

Symptoms of overdose include difficulty in breathing (severe), dizziness (severe), drowsiness (severe), muscle trembling, jerking, stiffness, or uncontrolled movements (severe), small pupils, unusual excitement, and unusual tiredness or weakness (severe).

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TWO CASE REPORTS DESCRIBING THE OCCURRENCE OF VOMITING IN 2 PATIENTS 9-YR OLD ABRUPTLY WITHDRAWN FROM DRUG.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/

SUBLETHAL DOSES PRODUCE ATAXIA & RESPIRATORY PARALYSIS IN ANIMALS WHILE LETHAL DOSES (IV) PRODUCE CONVULSIONS.

...IT CAN BE FETAL DEPRESSANT. CAUSES ANAL SPHINCTER RELAXATION IN A NUMBER OF SPECIES.

ELECTROPHYSIOLOGIC STUDIES...IN CATS, INDICATED CHLORPROTHIXENE REDUCED SPONTANEOUS RETINAL ACTIVITY, WHILE ONLY SLIGHTLY AFFECTING RESPONSES TO LIGHT STIMULI, & INCR POTENTIALS FROM VISUAL CORTEX.

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/

Hepatic

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.

Hepatic Half Life: 8 to 12 hours

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.

Incomplete bioavailability.

.../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.