Clozapine

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Names

[ Name ]:
Clozapine

[Synonym ]:
8-Chloro-11-(4-methyl-piperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine
Asaleptin
3-chloro-6-(4-methylpiperazin-1-yl)-5H-benzo[b][1,4]benzodiazepine
EINECS 227-313-7
8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[h,e][1,4]diazepine
8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepine
Clorazil
5H-Dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-
Clozapine
Clozapine (Tautomer)
Iprox
8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine
5H-Dibenzo[b,e][1,4]diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-
Clozapinum
Azaleptine
Clozaril
Clozapin
Leponex
Fazaclo
Lepotex
MFCD00153785
8-CHLORO-11-(4-METHYL-1-PIPERAZINYL)-5H-DIBENZO(B,E)(1,4)DIA - ZEPINE

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
489.2±55.0 °C at 760 mmHg

[ Melting Point ]:
182-185°C

[ Molecular Formula ]:
C₁₈H₁₉ClN₄

[ Molecular Weight ]:
326.823

[ Flash Point ]:
249.6±31.5 °C

[ Exact Mass ]:
326.129822

[ PSA ]:
30.87000

[ LogP ]:
2.36

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.681

[ Storage condition ]:
Store at RT

[ Water Solubility ]:
ethanol: 1 mg/mL

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: HP1750000

CHEMICAL NAME :: 5H-Dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-

CAS REGISTRY NUMBER :: 5786-21-0

BEILSTEIN REFERENCE NO. :: 0764984

LAST UPDATED :: 199807

DATA ITEMS CITED :: 33

MOLECULAR FORMULA :: C18-H19-Cl-N4

MOLECULAR WEIGHT :: 326.86

WISWESSER LINE NOTATION :: T C676 BM INJ FG J- AT6N DNTJ D1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 3280 mg/kg/82W-I

TOXIC EFFECTS :: Blood - agranulocytosis

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - child

DOSE/DURATION :: 4762 ug/kg

TOXIC EFFECTS :: Behavioral - ataxia Behavioral - muscle contraction or spasticity Behavioral - antipsychotic

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 5357 ug/kg/5D-I

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - antipsychotic Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 429 mg/kg/60D-I

TOXIC EFFECTS :: Behavioral - muscle contraction or spasticity

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 20 mg/kg

TOXIC EFFECTS :: Behavioral - coma Gastrointestinal - changes in structure or function of endocrine pancreas Blood - leukopenia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 280 mg/kg/5W-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), diffuse Blood - eosinophilia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 27 mg/kg/13D-I

TOXIC EFFECTS :: Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) Behavioral - hallucinations, distorted perceptions Behavioral - ataxia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human

DOSE/DURATION :: 5 mg/kg/7D-I

TOXIC EFFECTS :: Cardiac - pulse rate increase, without fall in BP

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 4286 ug/kg/11D-I

TOXIC EFFECTS :: Gastrointestinal - hypermotility, diarrhea Blood - changes in cell count (unspecified) Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 28 mg/kg/2W-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of endocrine pancreas

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 2211 mg/kg/37W-I

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other Enzymes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 270 mg/kg/6W-I

TOXIC EFFECTS :: Lungs, Thorax, or Respiration - structural or functional change in trachea or bronchi Gastrointestinal - hypermotility, diarrhea Blood - agranulocytosis

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 251 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 240 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 41600 ug/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intramuscular

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 210 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 150 mg/kg

TOXIC EFFECTS :: Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 90 mg/kg

TOXIC EFFECTS :: Behavioral - convulsions or effect on seizure threshold Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 194 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Behavioral - excitement

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 36500 ug/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 145 mg/kg

TOXIC EFFECTS :: Gastrointestinal - nausea or vomiting

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 510 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 900 mg/kg/30D-I

TOXIC EFFECTS :: Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3650 mg/kg/1Y-I

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Liver - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 6320 mg/kg/52W-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Gastrointestinal - changes in structure or function of salivary glands

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 14560 mg/kg/2Y-I

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Cardiac - other changes

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1080 mg/kg

SEX/DURATION :: female 16-22 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 24 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 96 mg/kg

SEX/DURATION :: female 9-14 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 48 mg/kg

SEX/DURATION :: female 7-12 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :: Sex chromosome loss and nondisjunction

MUTATION DATA

TYPE OF TEST :: Cytogenetic analysis

TEST SYSTEM :: Human Lymphocyte

DOSE/DURATION :: 10 mg/L

REFERENCE :: HUGEDQ Human Genetics. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.31- 1976- Volume(issue)/page/year: 38,77,1977 *** REVIEWS *** TOXICOLOGY REVIEW PBPSDY Pharmacological and Biochemical Properties of Drug Substances. (American Pharmaceutical Assoc., 2215 Constitution Ave., NW, Washington, DC 20037) V.1- 1977- Volume(issue)/page/year: 1,1,1977

Safety Information

[ Symbol ]:

GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H301-H341-H361

[ Precautionary Statements ]:
Missing Phrase - N15.00950417-P280

[ Hazard Codes ]:
Xi:Irritant

[ Risk Phrases ]:
R22;R36/37/38

[ Safety Phrases ]:
S26

[ RIDADR ]:
UN 2811 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
HP1750000

[ Packaging Group ]:
III

[ Hazard Class ]:
6.1(b)

[ HS Code ]:
2933990090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

methylpiperazine
8-Chloro-11-oxo-10,11-dihydro-5H-dibenzo-1,4-diazepine
[2-(2-amino-4-chloroanilino)phenyl]-(4-methylpiperazin-1-yl)methanone
8,11-Dichloro-5H-dibenzo[b,e][1,4]diazepine
(4-chloro-2-nitrophenyl)-(2-cyanophenyl)-amine
Benzoicacid, 2-[(2-amino-4-chlorophenyl)amino]-

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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