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Thiopropazate

Thiopropazate structure

Thiopropazate 

structure
  • CAS No:

    84-06-0

  • Formula:

    C23H28ClN3O2S

  • Chemical Name:

    Thiopropazate

  • Synonyms:

    1-Piperazineethanol,4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-,1-acetate;1-Piperazineethanol,4-[3-(2-chlorophenothiazin-10-yl)propyl]-,acetate (ester);1-Piperazineethanol,4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl]-,acetate (ester);1-Piperazineethanol,4-[3-(2-chlorophenothiazin-10-yl)propyl]-,acetate;N-(β-Acetoxyethyl)-N′-[γ-(2′-chloro-10′-phenothiazinyl)propyl]piperazine;1-(2-Acetoxyethyl)-4-[3-(2-chloro-10-phenothiazinyl)propyl]piperazine;10-[3-[4-(2-Acetoxyethyl)-1-piperazinyl]propyl]-2-chlorophenothiazine;2-Chloro-10-[3-[1-(2-acetoxyethyl)-4-piperazinyl]propyl]phenothiazine;Dartalan;Thiopropazate;Dartal;Thiopropazat;Perphenazine acetate

Description

Thiopropazate is a typical antipsychotic of the phenothiazine class. It is a prodrug to Perphenazine. Perphenazine is a typical antipsychotic drug.


Thiopropazate is a phenothiazine derivative in which 10H-phenothiazine has a chloro subsitituent at the 2-position and a 3-[4-(2-acetoxyethyl)piperazin-1-yl]propyl group at N-10. It has a role as a phenothiazine antipsychotic drug and a dopaminergic antagonist. It is a member of phenothiazines, a N-alkylpiperazine, an acetate ester and an organochlorine compound.

Thiopropazate Basic Attributes

446.006

446.01

201-513-4

0JFY081Q2X

DTXSID6023654

N - Nervous system

Characteristics

61.3

4.45430

1.234g/cm3

MP: 167-169 °C /DIMALEATE/

214-218 °C @ Press: 0.1 Torr

307.3ºC

1.6

SOL IN ETHER

PKA= 7.3

DECOMP BETWEEN 223-229 °C /DIHYDROCHLORIDE/|SADTLER REFERENCE NUMBER: 691 /DIHYDROCHLORIDE/|CRYSTALS FROM 95% ETHANOL /DIHYDROCHLORIDE/|CRYSTALS FROM METHANOL + ETHANOL /DIMALEATE/|WHITE, CRYSTALLINE POWDER /DIHYDROCHLORIDE/

Safety Information

SENSITIVE TO LIGHT; UNSTABLE IN HEAT /DIHYDROCHLORIDE/

Toxicity

...POTENTIATES THE ACTIONS OF BARBITURATES. /DIHYDROCHLORIDE/|...POTENTIALLY DANGEROUS SEIZURES MAY OCCUR /WITH PIPERAZINE & THIOPROPAZATE HYDROCHLORIDE/.|...LEVODOPA & /THIOPROPAZATE/...MAY BLOCK THE EFFECTS OF EACH OTHER WHEN THESE DRUGS ARE ADMIN TOGETHER. /DIHYDROCHLORIDE/|/THIOPROPAZATE/...MAY BE ABLE TO REVERSE THE ANTIHYPERTENSIVE ACTIVITY OF GUANETHIDINE. /DIHYDROCHLORIDE/|For more Interactions (Complete) data for THIOPROPAZATE (7 total), please visit the HSDB record page.

Drug Information

Antipsychotic Agents, Phenothiazine|A PIPERAZINE PHENOTHIAZINE FOR MANAGEMENT OF ACUTE & CHRONIC PSYCHOSES. /DIHYDROCHLORIDE/

PHENOTHIAZINES SHOULD BE USED WITH EXTREME CAUTION, IF @ ALL, IN UNTREATED EPILEPTIC PT & IN PT UNDERGOING WITHDRAWAL FROM CENTRAL DEPRESSANT DRUGS SUCH AS ALC & BARBITURATES. PHENOTHIAZINES MAY BE USED IN EPILEPTICS IF CONCOMITANT ANTICONVULSANT DRUG THERAPY IS MAINTAINED. /PHENOTHIAZINES/|...PRECAUTIONS SHOULD BE OBSERVED IN USE OF PHENOTHIAZINES FOR NAUSEA & VOMITING AS WITH USE OF POTENT ANALGESICS IN TREATMENT OF PAIN, BECAUSE THEY MAY MASK DIAGNOSTIC SYMPTOMS IN ACUTE SURGICAL CONDITIONS OR NEUROLOGICAL SYNDROMES. /PHENOTHIAZINES/|EXTRAPYRAMIDAL SYMPTOMS OCCUR FREQUENTLY. /DIHYDROCHLORIDE/

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

TOLERANCE TO VARIOUS ANTIPSYCHOTIC DRUGS & CROSS-TOLERANCE AMONG AGENTS... DEMONSTRABLE IN BEHAVIORAL & BIOCHEM EXPT IN ANIMALS, /ESP/...THOSE DIRECTED TOWARD EVALUATION OF BLOCKADE OF DOPAMINERGIC RECEPTORS IN BASAL GANGLIA. /PHENOTHIAZINES/|ONE CORRELATE OF TOLERANCE...IS DEVELOPMENT OF DISUSE SUPERSENSITIVITY IN /FOREBRAIN DOPAMINERGIC/...SYSTEMS... THIS MECHANISM MAY UNDERLIE... WITHDRAWAL-EMERGENT DYSKINESIAS (DEVELOPMENT OF CHOREOATHETOSIS ON ABRUPT DISCONTINUATION OF ANTIPSYCHOTIC DRUGS, ESP FOLLOWING PROLONGED USE OF HIGH DOSES... /PHENOTHIAZINES/

APPROX HALF OF METABOLITES OF COMMONLY USED PHENOTHIAZINES ARE FOUND IN URINE & REST IN FECES. 6 MO AFTER DISCONTINUATION OF THESE DRUGS, VARIOUS METABOLITES ARE DETECTABLE IN URINE. /PHENOTHIAZINES/|PHENOTHIAZINE TRANQUILIZERS CROSS PLACENTA RAPIDLY, & THEY HAVE BEEN MEASURED...IN URINE & TISSUES OF NEONATES OF TREATED MOTHERS, BUT VERY LOW BLOOD LEVELS OF MOTHERS & FETUSES HAVE BEEN MEASURED ONLY RECENTLY... /PHENOTHIAZINES/

...METAB...BY OXIDATIVE PROCESSES MEDIATED LARGELY BY HEPATIC MICROSOMAL & OTHER DRUG-METABOLIZING ENZYMES. CONJUGATION WITH GLUCURONIC ACID...PROMINENT ROUTE.../PRC: REACTIONS INCL HYDROXYLATION, DEMETHYLATION, SULFOXIDE FORMATION; METABOLIC ALTERATIONS IN SIDE CHAIN MAY ALSO OCCUR. /PHENOTHIAZINES/

THERE IS AN ADENYLATE CYCLASE IN LIMBIC SYSTEM, AS WELL AS IN CAUDATE NUCLEUS, THAT IS SPECIFICALLY ACTIVATED BY DOPAMINE. ...ACTIVATION OF...ENZYME IS... BLOCKED BY...PHENOTHIAZINES. ...THERAPEUTIC EFFICACY & SIDE EFFECTS MAY RELATE TO INHIBITION OF DOPAMINE ACTIVATION OF ADENYLATE CYCLASE. /PHENOTHIAZINES/

PHENOTHIAZINES INHIBIT EJACULATION WITHOUT INTERFERING WITH ERECTION. /PHENOTHIAZINES/|MOST DANGEROUS EFFECTS OF PHENOTHIAZINES ARE THOSE RESULTING FROM HYPERSENSITIVITY REACTIONS, PARTICULARLY BLOOD DYSCRASIAS. THERAPEUTIC DOSES... MAY CAUSE FAINTNESS, PALPITATION, NASAL STUFFINESS, DRY MOUTH, & SOME SLIGHT CONSTIPATION. PT MAY COMPLAIN OF BEING COLD, DROWSY, OR WEAK. /PHENOTHIAZINES/|MOST TROUBLESOME SIDE EFFECT IS ORTHOSTATIC HYPOTENSION, WHICH MAY RESULT IN SYNCOPE. ... THERE IS GENERAL AGREEMENT THAT JAUNDICE FOLLOWING PHENOTHIAZINE ADMIN IS HYPERSENSITIVITY REACTION. ... LEUKOCYTOSIS, LEUKOPENIA, & EOSINOPHILIA OCCUR WITH PHENOTHIAZINE MEDICATION. /PHENOTHIAZINES/|DERMATOLOGICAL REACTIONS TO PHENOTHIAZINES ARE NOT UNCOMMON. ... PHOTOSENSITIVITY OCCURS...RESEMBLING THAT SEEN WITH SEVERE SUNBURN. /PHENOTHIAZINES/|For more Human Toxicity Excerpts (Complete) data for THIOPROPAZATE (7 total), please visit the HSDB record page.

thiopropazate

Thiopropazate Use and Manufacturing

Methods of Manufacturing

FROM 2-CHLORO-10-(GAMMA-CHLOROPROPYL)-PHENOTHIAZINE & PIPERAZINE IN BUTANONE FOLLOWED BY TREATMENT WITH BETA-BROMOETHYL ACETATE IN TOLUENE: CUSIC, US PATENT 2,766,235 (1956); ANDERSON ET AL, ARZNEIMITTEL-FORSCH 12, 937 (1962).|10-(3-CHLOROPROPYL) PHENOTHIAZINE IS CONDENSED WITH PIPERAZINE IN BUTANONE SOLN &...CONDENSED WITH 2-BROMOETHYL ACETATE WITH...SUITABLE DEHYDROBROMINATING AGENT SUCH AS SODAMIDE TO FORM THIOPROPAZATE. REACTION OF BASE WITH DOUBLE MOLAR PORTION OF HYDROGEN CHLORIDE YIELDS THE SALT. /DIHYDROCHLORIDE/

DARTAL, DARTALAN. /DIHYDROCHLORIDE/

A FEW AVAIL AGENTS...ARE NOW KNOWN TO HAVE INFERIOR ANTIPSYCHOTIC EFFECTS OR... ARE NO LONGER COMMONLY USED IN PSYCHIATRIC PT. THESE INCL...THIOPROPAZATE (DARTAL).

Pharmaceuticals

Computed Properties

Molecular Weight:446.0
XLogP3:4.8
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:8
Exact Mass:445.1590760
Monoisotopic Mass:445.1590760
Topological Polar Surface Area:61.3
Heavy Atom Count:30
Complexity:561
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

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