10-(3-(4-Methyl-1-piperazinyl)-propyl)-2-(trifluor-methyl)-10H-phenothiazin

DEA NFLIS-Drug Category -> Depressants and Tranquilizers

Pharmaceuticals -> Nervous system -> Antipsychotics

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antipsychotics

log Kow= 5.03 @ 25 °C

4.9

4.71

Freely sol in water /Dihydrochloride/

FREELY SOL IN WATER; SOL IN ALCOHOL; SPARINGLY SOL IN CHLOROFORM; INSOL IN ETHER & BENZENE /HYDROCHLORIDE/

In water, 12.2 mg/l @ 25 °C

8.76e-03 g/L

Breast Feeding; Lactation; Milk, Human; Antipsychotic Agents; Phenothiazines

Pharmaceuticals

Cream-colored, fine powder from absolute alcohol; MP: 242-243 °C; pH of 5% aq soln= 2.2, Hygroscopic /Dihydrochloride/

MP: 193-194 °C; crystals from alcohol /Dimaleate/

MP: 173-175 °C /Sulfoxide dihydrochloride trihydrate/

188.1 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

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

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).

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Treatment is essentially symptomatic and supportive. Early gastric lavage is helpful. Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage. Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus. Extrapyramidal symptoms may be treated with anti-parkinsonism drugs, barbiturates or Benadryl. See prescribing information for these products. Care should be taken to avoid increasing respiratory depression. If administration of a stimulant is desirable, amphetamine, dextroamphetamine or caffeine with sodium benzoate is recommended. Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided. If hypotension occurs, the standard measures for managing circulatory shock should be initiated. If it is desirable to administer a vasoconstrictor, Levophed and Neo-Synephrine are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause a further lowering of blood pressure. (L1712)

Additive QT interval prolongation may increase the risk of ventricular tachycardia when /probucol is used with phenothiazines/. /Phenothiazines/

Concurrent use /of other photosensitizing medications/ with phenothiazines may cause additive photosensitizing effects. In addition, concurrent use of systemic methoxsalen, trixsalen, or tetracyclines with phenothiazines may potentiate intraocular photochemical damage to the choroid, retina, or lens. /Phenothiazines/

Prior administration of phenothiazines may decrease the pressor effect and shorten the duration of action of phenylephrine. /Phenothiazines/

In addition to increased CNS and respiratory depression, concurrent use /of opiod (narcotic) analgesics/ with phenothiazines increases orthostatic hypotension and increases the risk of severe constipation, which may lead to paralytic ileus, and/or urinary retention. /Phenothiazines/

For more Interactions (Complete) data for TRIFLUOPERAZINE (29 total), please visit the HSDB record page.

Liver test abnormalities have been reported to occur in a high proportion of patients on long term phenothiazine therapy, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury, resembling that due to chlorpromazine, have been reported with trifluoperazine therapy. The onset of jaundice is usually within 1 to 4 weeks, and the pattern of serum enzyme elevations is typically cholestatic or mixed. Immunoallergic features (rash, fever and eosinophilia) were present in some cases but were mild and self-limited; autoantibodies were rare.

Trifluoperazine 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.

EPITHELIAL KERATOPATHY OFTEN IS OBSERVED IN PATIENTS ON LONG-TERM THERAPY WITH CHLORPROMAZINE, AND OPACITIES IN THE CORNEA AND IN THE LENS OF THE EYE ALSO HAVE BEEN NOTED. ... PIGMENTARY RETINOPATHY HAS BEEN REPORTED, PARTICULARLY FOLLOWING DOSES OF THIORIDAZINE IN EXCESS OF 1000 MG/DAY; A MAXIMUM DAILY DOSE OF 800 MG CURRENTLY IS RECOMMENDED. /PHENOTHIAZINES/

...OCULOGYRIC CRISES CAN BE PRODUCED... BLURRING OF VISION HAS BEEN MENTIONED OCCASIONALLY, ASSOC WITH DRYNESS OF MOUTH, WHICH SUGGESTS THAT BLURRING MIGHT BE DUE TO ANTICHOLINERGIC MYDRIASIS & CYCLOPLEGIA. ...SUSPICIONS...THAT TRIFLUOPERAZINE PRODUCES DEPOSITS IN LENS OR CORNEA.

LARGE DOSES (80 MG TRIFLUOPERAZINE) ARE MORE LIKELY TO PRODUCE OR AGGRAVATE DYSKINESIA IN PT AGE 40-55 THAN ARE CONVENTIONAL DOSES. RISK OF PERSISTENT MOTOR ABNORMALITIES RISES SHARPLY IN OLDER PERSONS WITH CHRONIC DOSING OF 100-200 MG CHLORPROMAZINE OR EQUIV.

Most studies indicate the phenothiazines are nonteratogenic but there are reports of defects in infants exposed to these drugs during the first trimester. /Phenothiazines/

For more Human Toxicity Excerpts (Complete) data for TRIFLUOPERAZINE (7 total), please visit the HSDB record page.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

trifluoperazine

Stelazine

Antipsychotics

2

less-DILI-concern drugs

... TRIFLUOPERAZINE HAS A HIGH TENDENCY TO PRODUCE EXTRAPYRAMIDAL EFFECTS ... EXTRAPYRAMIDAL SYMPTOMS PRESENTING AS TORTICOLLIS, STIFFENING OF THE BODY, SPASTICITY, IMPAIRED SPEECH, AND OPISTHOTONOS MAY OCCUR. THESE SYMPTOMS MAY OCCUR FREQUENTLY IN CHILDREN WHO HAVE BEEN ADMINISTERED PROCHLORPERAZINE (cOMPAZINE) FOR THE TREATMENT OF NAUSEA AND VOMITING. /PHENOTHIAZINES/

EXTRAPYRAMIDAL SYMPTOMS...RELIEVED WITH BARBITURATES, METHYLPHENIDATE HYDROCHLORIDE...ANTI-PARKINSON DRUGS...BENZTROPINE MESYLATE...TRIHEXYPHENIDYL HYDROCHLORIDE...DIPHENHYDRAMINE HYDROCHLORIDE...IN SEVERE CASES, SUPPORTIVE THERAPY...MAINTAINING CLEAR AIRWAY & ADEQUATE HYDRATION. /HYDROCHLORIDE/

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).

N - Nervous system

QN - Nervous system

Trifluoperazine is a trifluoro-methyl phenothiazine derivative intended for the management of schizophrenia and other psychotic disorders. Trifluoperazine has not been shown effective in the management of behaviorial complications in patients with mental retardation.

Trifluoperazine 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.

...PHENOTHIAZINES, BLOCK DOPAMINE RECEPTORS & INCR TURNOVER RATE OF DOPAMINE IN CORPUS STRIATUM. INCR TURNOVER RATE IS BELIEVED TO BE RESULT OF NEURONAL FEEDBACK MECHANISM. ...OF IDENTIFIED DOPAMINERGIC NEURONS IN SUBSTANTIA NIGRA & VENTRAL TEGMENTAL AREAS. SPONTANEOUS FIRING OF THESE CELLS IS INCR... /PHENOTHIAZINES/

Hepatic.

AFTER CHRONIC ADMIN OF PIPERAZINE-SUBSTITUTED PHENOTHIAZINE DRUGS...TO RATS, TISSUES CONTAINED DRUG METABOLITES, IN WHICH PIPERAZINE RING FISSION BY MULTIPLE OXIDATIVE N-DEALKYLATION HAD OCCURRED TO GIVE SUBSTITUTED ETHYLENEDIAMINE. ...2-TRIFLUOROMETHYL ANALOGUE WAS FORMED SIMILARLY FROM TRIFLUPERAZINE.

IN VIVO DEGRADATION OF PIPERAZINE RING OF TRIFLUOPERAZINE LEADS TO FORMATION OF GAMMA-(PHENOTHIAZINYL-10)-PROPYLAMINE & ITS RING SUBSTITUTED ANALOGS CF3- & CL-. SULFOXIDES OF THESE METABOLITES HAVE BEEN IDENTIFIED AS URINARY BIOTRANSFORMATION PRODUCTS IN RATS (CHRONIC).

Hepatic. Half Life: 10-20 hours

214IZI85K3

TRIFLUOPERAZINE

Established Pharmacologic Class [EPC] - Phenothiazine

Chemical Structure [CS] - Phenothiazines

Trifluoperazine is a Phenothiazine.

Drugs used to prevent NAUSEA or VOMITING.

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.

Antipsychotic

For the treatment of anxiety disorders, depressive symptoms secondary to anxiety and agitation.

TABLET: 1, 2, 5, 10 MG; CAPSULE: 10 MG/ML; VIAL: 2 MG/ML IN 10 ML. /FROM TABLE, HYDROCHLORIDE/

SYRUP NF: 10 MG/ML /HYDROCHLORIDE/

THE NATURE OF SUBSTITUENT @ POSITION 10 ALSO INFLUENCES PHARMACOLOGICAL ACTIVITY. ... SEVERAL POTENT PHENOTHIAZINE ANTIPSYCHOTIC COMPOUNDS HAVE A PIPERAZINE (OR PIPERAZINYL) GROUP IN THE SIDE CHAIN; ... TRIFLUOPERAZINE /IS AN/ EXAMPLE.

Phenothiazine has a three-ring structure in which two benzene rings are linked by a sulfur and a nitrogen atom. If the nitrogen at position 10 is replaced by a carbon atom with a double bond to the side chain, the compound is a thioxanthene. /PHENOTHIAZINES/