Product Name

  • Name

    Clozapine

  • EINECS 227-313-7
  • CAS No. 5786-21-0
  • Article Data19
  • CAS DataBase
  • Density 1.319 g/cm3
  • Solubility ethanol: 1 mg/mL
  • Melting Point 182-185 °C
  • Formula C18H19ClN4
  • Boiling Point 489.159 °C at 760 mmHg
  • Molecular Weight 326.829
  • Flash Point 249.635 °C
  • Transport Information UN 2811 6.1/PG 3
  • Appearance Yellow Crystalline Solid
  • Safety 26
  • Risk Codes 22-36/37/38
  • Molecular Structure Molecular Structure of 5786-21-0 (Clozapine)
  • Hazard Symbols HarmfulXn, IrritantXi
  • Synonyms Clorazil;Fazaclo;Iprox;Clozapina [INN-Spanish];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)-;Leponex;Asaleptin;Clozaril (TN);Clozapine [USAN:BAN:INN];8-chloro-11（4-methy-1-piperaziong）-5-H-dibenzo[b,e][1.4]diazepine;
  • PSA 30.87000
  • LogP 3.17210

Synthetic route

clozapine N-oxide

clozapine N-oxide

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With hydrogenchloride; titanium(III) chloride In water; acetonitrile at 20℃; for 1h;97%
1-methyl-piperazine
109-01-3

1-methyl-piperazine

8-chloro-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one
50892-62-1

8-chloro-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With titanium tetrachloride In 1,4-dioxane; toluene for 2h; Heating;88%
With titanium tetrachloride53%
With hydrogenchloride; titanium tetrachloride In water; methoxybenzene; isopropyl alcohol; toluene
With titanium tetrachloride
clozapine N-oxide

clozapine N-oxide

(2E)-3-phenyl-2-propen-1-ol
4407-36-7

(2E)-3-phenyl-2-propen-1-ol

A

1-phenyl-propane-1,2,3-triol
63157-81-3

1-phenyl-propane-1,2,3-triol

B

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With osmium(VIII) oxide In water; tert-butyl alcohol at 20℃; for 19h; Inert atmosphere;A 73%
B 84%
...Expand
N-(4-chloro-2-nitrophenyl)-N-{2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amine
65514-72-9

N-(4-chloro-2-nitrophenyl)-N-{2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amine

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With tributylphosphine at 150℃; for 48h; Temperature; Reagent/catalyst;80%
Multi-step reaction with 2 steps
1: 3 h / 150 °C
2: triphenylphosphine / 230 °C
View Scheme
N-{4-chloro-2-[(triphenylphosphoranylidene)amino]phenyl}-N-{2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amine

N-{4-chloro-2-[(triphenylphosphoranylidene)amino]phenyl}-N-{2-[(4-methylpiperazin-1-yl)carbonyl]phenyl}amine

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With triphenylphosphine at 230℃;65%
styrene
292638-84-7

styrene

clozapine N-oxide

clozapine N-oxide

A

phenylethane 1,2-diol
93-56-1

phenylethane 1,2-diol

B

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With osmium(VIII) oxide In water; tert-butyl alcohol at 20℃; for 19h; Inert atmosphere;A 8%
B 53%
...Expand
4-Chloro-2-nitroaniline
89-63-4

4-Chloro-2-nitroaniline

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: o-xylene / Dean-Stark
1.2: Reflux
2.1: iron; calcium chloride / water / 90 - 100 °C
3.1: triethylamine / dichloromethane / 0.33 h / 20 °C
3.2: 2.33 h / 20 °C
4.1: titanium tetrachloride / o-xylene / 10 - 15 °C / Reflux
5.1: titanium tetrachloride / 10 °C / Reflux
View Scheme
Multi-step reaction with 6 steps
1.2: 12 h / 20 °C / Reflux
2.1: iodine / 3 h / 50 - 55 °C
3.1: sodium dithionate / methanol / 2 h / 50 - 55 °C
4.1: toluene / 0 - 5 °C
5.1: trichlorophosphate / 3 h / Reflux
6.1: potassium carbonate / ethanol / 3 h / Reflux
View Scheme
bromobenzene
108-86-1

bromobenzene

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1.2: 12 h / 20 °C / Reflux
2.1: iodine / 3 h / 50 - 55 °C
3.1: sodium dithionate / methanol / 2 h / 50 - 55 °C
4.1: toluene / 0 - 5 °C
5.1: trichlorophosphate / 3 h / Reflux
6.1: potassium carbonate / ethanol / 3 h / Reflux
View Scheme
N-(4-chloro-2-nitrophenyl)benzenamine
16611-15-7

N-(4-chloro-2-nitrophenyl)benzenamine

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: iodine / 3 h / 50 - 55 °C
2: sodium dithionate / methanol / 2 h / 50 - 55 °C
3: toluene / 0 - 5 °C
4: trichlorophosphate / 3 h / Reflux
5: potassium carbonate / ethanol / 3 h / Reflux
View Scheme
ortho-chlorobenzoic acid
118-91-2

ortho-chlorobenzoic acid

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1.1: o-xylene / Dean-Stark
1.2: Reflux
2.1: iron; calcium chloride / water / 90 - 100 °C
3.1: triethylamine / dichloromethane / 0.33 h / 20 °C
3.2: 2.33 h / 20 °C
4.1: titanium tetrachloride / o-xylene / 10 - 15 °C / Reflux
5.1: titanium tetrachloride / 10 °C / Reflux
View Scheme
N-(4-chloro-2-nitrophenyl)-N-phenylacetamide

N-(4-chloro-2-nitrophenyl)-N-phenylacetamide

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: sodium dithionate / methanol / 2 h / 50 - 55 °C
2: toluene / 0 - 5 °C
3: trichlorophosphate / 3 h / Reflux
4: potassium carbonate / ethanol / 3 h / Reflux
View Scheme
N-(4-chloro-2-aminophenyl)-N-phenylacetamide

N-(4-chloro-2-aminophenyl)-N-phenylacetamide

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: toluene / 0 - 5 °C
2: trichlorophosphate / 3 h / Reflux
3: potassium carbonate / ethanol / 3 h / Reflux
View Scheme
N-(2-(N-phenylacetamido)-5-chlorophenyl)-4-methylpiperazine-1-carboxamide

N-(2-(N-phenylacetamido)-5-chlorophenyl)-4-methylpiperazine-1-carboxamide

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: trichlorophosphate / 3 h / Reflux
2: potassium carbonate / ethanol / 3 h / Reflux
View Scheme
N-acetyl clozapine

N-acetyl clozapine

clozaril
5786-21-0

clozaril

Conditions
ConditionsYield
With potassium carbonate In ethanol for 3h; Reflux;5 g
2-(2-methylphenyl)pyridine
10273-89-9

2-(2-methylphenyl)pyridine

clozaril
5786-21-0

clozaril

C30H29N5

C30H29N5

Conditions
ConditionsYield
With C17H24N5Ru(1+)*F6P(1-); potassium acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 35℃; for 48h; Inert atmosphere;96%
clozaril
5786-21-0

clozaril

clozapine N-oxide

clozapine N-oxide

Conditions
ConditionsYield
Stage #1: clozaril With 3-chloro-benzenecarboperoxoic acid In methanol at 23℃; for 0.166667h; Inert atmosphere;
Stage #2: With triethylamine In methanol for 0.166667h; Inert atmosphere;		94%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 0.166667h;
mesitylenesulfonylhydroxylamine
36016-40-7

mesitylenesulfonylhydroxylamine

clozaril
5786-21-0

clozaril

1-amino-4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylhexahydropyrazin-1-ium 2,4,6-trimethyl-1-benzenesulfonate

1-amino-4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylhexahydropyrazin-1-ium 2,4,6-trimethyl-1-benzenesulfonate

Conditions
ConditionsYield
In dichloromethane at 0℃; for 0.333333h;82%
ethyl 5-bromovalerate
14660-52-7

ethyl 5-bromovalerate

clozaril
5786-21-0

clozaril

C25H31ClN4O2

C25H31ClN4O2

Conditions
ConditionsYield
With potassium tert-butylate In N,N-dimethyl-formamide at 20℃;80%
carbon dioxide
124-38-9

carbon dioxide

clozaril
5786-21-0

clozaril

C19H19N5

C19H19N5

Conditions
ConditionsYield
With nickel(II) acetylacetonate; potassium fluoride; phenylsilane; ammonia; zinc; bis(2-diphenylphosphinoethyl)phenylphosphine In 1-methyl-pyrrolidin-2-one at 90 - 140℃; under 760.051 Torr; for 20h; Sealed tube;80%
N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide
82626-48-0

N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide

clozaril
5786-21-0

clozaril

C37H39N7O

C37H39N7O

Conditions
ConditionsYield
With C17H24N5Ru(1+)*F6P(1-); potassium acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 35℃; for 144h; Reagent/catalyst; Inert atmosphere;76%
With C17H24N5Ru(1+)*F6P(1-); potassium acetate; potassium carbonate In 1-methyl-pyrrolidin-2-one at 35℃; for 144h; Inert atmosphere; Glovebox;76%
clozaril
5786-21-0

clozaril

N-desmethylclozapine
6104-71-8

N-desmethylclozapine

Conditions
ConditionsYield
Stage #1: clozaril With carbonochloridic acid 1-chloro-ethyl ester In 1,2-dicholoroethane at 0℃; for 22.5h; Inert atmosphere; Reflux;
Stage #2: With methanol at 50℃; for 2h; Inert atmosphere;		69%
Stage #1: clozaril With carbonochloridic acid 1-chloro-ethyl ester In 1,2-dichloro-ethane for 24h; Reflux;
Stage #2: With methanol at 50℃; for 2h;
With cytochrome P450 1A2; cytochrome P450 3A4
clozaril
5786-21-0

clozaril

bis(pinacol)diborane
73183-34-3

bis(pinacol)diborane

11-(4-methylpiperazin-1-yl)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-dibenzo[b,e][1,4]diazepine

11-(4-methylpiperazin-1-yl)-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-dibenzo[b,e][1,4]diazepine

Conditions
ConditionsYield
With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; XPhos In 1,4-dioxane at 110℃; for 12h; Inert atmosphere; Sealed tube;59%
clozaril
5786-21-0

clozaril

methyl iodide
74-88-4

methyl iodide

4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1,1-dimethylpiperazin-1-ium iodide

4-(8-chloro-5H-dibenzo[b,e][1,4]diazepin-11-yl)-1,1-dimethylpiperazin-1-ium iodide

Conditions
ConditionsYield
In acetone at 20℃;55%
n-decanoyl chloride
112-13-0

n-decanoyl chloride

clozaril
5786-21-0

clozaril

1-[8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepin-5-yl]decan-1-one
1357146-74-7

1-[8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepin-5-yl]decan-1-one

Conditions
ConditionsYield
With pyridine; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;36%
clozaril
5786-21-0

clozaril

A

7-Hydroxyclozapine
355004-92-1

7-Hydroxyclozapine

B

C18H19ClN4O
1239601-19-4

C18H19ClN4O

Conditions
ConditionsYield
Stage #1: clozaril With ethylenediaminetetraacetic acid trisodium salt; oxygen; manganese (II) acetate tetrahydrate; ascorbic acid In water pH=4; Udenfriend reaction;
Stage #2: With ferrous(II) sulfate heptahydrate; ethylenediaminetetraacetic acid trisodium salt; oxygen In water at 45℃; for 2h; Udenfriend reaction;		A 4.93%
B 2.98%
GLUTATHIONE
70-18-8

GLUTATHIONE

clozaril
5786-21-0

clozaril

A

C-6 glutathionyl clozapine

C-6 glutathionyl clozapine

B

C-9 glutathionyl clozapine

C-9 glutathionyl clozapine

Conditions
ConditionsYield
With horseradish peroxidase type VI; dihydrogen peroxide In phosphoric acid at 25℃; for 4h; pH=7.4; Oxidation; Enzymatic reaction;
With sodium hypochlorite In ethanol; water Oxidation;
...Expand
clozaril
5786-21-0

clozaril

clozapine nitrenium ion

clozapine nitrenium ion

Conditions
ConditionsYield
With hypochloric acid In water at 25℃; pH=6; Kinetics; Oxidation;
1-hydroxy-pyrrolidine-2,5-dione
6066-82-6

1-hydroxy-pyrrolidine-2,5-dione

N-acetylcystein
616-91-1

N-acetylcystein

clozaril
5786-21-0

clozaril

keyhole limpet hemocyanin

keyhole limpet hemocyanin

clozapine-N-acetylcystein-modified keyhole limpet hemocyanin

clozapine-N-acetylcystein-modified keyhole limpet hemocyanin

Conditions
ConditionsYield
Stage #1: N-acetylcystein; clozaril With sodium hypochlorite In ethanol for 0.166667h; pH=4.0;
Stage #2: 1-hydroxy-pyrrolidine-2,5-dione With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide; acetonitrile
Stage #3: keyhole limpet hemocyanin In phosphate buffer; acetonitrile at 20℃; for 1h; pH=8.0;
...Expand
1-hydroxy-pyrrolidine-2,5-dione
6066-82-6

1-hydroxy-pyrrolidine-2,5-dione

N-acetylcystein
616-91-1

N-acetylcystein

clozaril
5786-21-0

clozaril

rabbit serum albumin

rabbit serum albumin

clozapine-N-acetylcystein-modified rabbit serum albumin

clozapine-N-acetylcystein-modified rabbit serum albumin

Conditions
ConditionsYield
Stage #1: N-acetylcystein; clozaril With sodium hypochlorite In ethanol for 0.166667h; pH=4.0;
Stage #2: 1-hydroxy-pyrrolidine-2,5-dione With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide; acetonitrile
Stage #3: rabbit serum albumin In phosphate buffer; acetonitrile at 20℃; for 1h; pH=8.0;
...Expand
clozaril
5786-21-0

clozaril

8-chloro-11-(4-methylpiperazin-1-yl)-5-nitroso-5H-dibenzo[b,e][1,4]diazepine
156632-03-0

8-chloro-11-(4-methylpiperazin-1-yl)-5-nitroso-5H-dibenzo[b,e][1,4]diazepine

Conditions
ConditionsYield
With isopentyl nitrite In dichloromethane
With isopentyl nitrite In dichloromethane at 20℃; for 3h;
clozaril
5786-21-0

clozaril

8-chloro-11-(4-methyl-piperazin-1-yl)-5-nitro-5H-dibenzo[b,e][1,4]diazepine

8-chloro-11-(4-methyl-piperazin-1-yl)-5-nitro-5H-dibenzo[b,e][1,4]diazepine

Conditions
ConditionsYield
With isopentyl nitrite In dichloromethane at 20℃; for 3h;
clozaril
5786-21-0

clozaril

8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepin-5-amine
136772-01-5

8-chloro-11-(4-methylpiperazin-1-yl)-5H-dibenzo[b,e][1,4]diazepin-5-amine

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: isoamyl nitrite / CH2Cl2
2: AcOH; Zn
View Scheme
Multi-step reaction with 2 steps
1: isoamyl nitrite / CH2Cl2 / 3 h / 20 °C
2: 0.84 g / Zn; AcOH / 3 h
View Scheme
Multi-step reaction with 2 steps
1: isopentyl nitrite / dichloromethane / 3 h / 20 °C
2: acetic acid; zinc / 4 h / 10 - 15 °C
View Scheme
Stage #1: clozaril With isopentyl nitrite In dichloromethane at 27℃; for 3h;
Stage #2: With acetic acid; zinc at 10 - 15℃; for 1h;
clozaril
5786-21-0

clozaril

N-[8-chloro-11-(4-methyl-piperazin-1-yl)-dibenzo[b,e][1,4]diazepin-5-yl]-nicotinamide

N-[8-chloro-11-(4-methyl-piperazin-1-yl)-dibenzo[b,e][1,4]diazepin-5-yl]-nicotinamide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1.1: isoamyl nitrite / CH2Cl2 / 3 h / 20 °C
2.1: 0.84 g / Zn; AcOH / 3 h
3.1: Argopore-CHO resin; NaBH3CN; AcOH
3.2: Et3N
3.3: TFA
View Scheme

Clozapine Chemical Properties

Empirical Formula: C18H19ClN4
Molecular Weight: 326.8233 g/mol
EINECS: 227-313-7 
Index of Refraction: 1.681
Density: 1.31 g/cm3
Flash Point: 249.6 °C
Melting point: 182-185 °C
Solubility: Ethanol: 1 mg/mL
Appearance: Yellow crystalline solid
Enthalpy of Vaporization: 75.54 kJ/mol
Boiling Point: 489.2 °C at 760 mmHg
Vapour Pressure: 1.02E-09 mmHg at 25 °C
Structure of Clozapine (CAS NO.5786-21-0):
                     
IUPAC Name: 3-Chloro-6-(4-methylpiperazin-1-yl)-5H-benzo[c][1,5]benzodiazepine
Product Category: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Dopamine receptor

Clozapine History

 Clozapine (CAS NO.5786-21-0) by Sandoz in 1961, and introduced in Europe in 10 years. In 1975, the report of agranulocytosis leading to death in some patients treated with clozapine, clozapine manufacturers to voluntarily withdraw. Clozapine fell out of favor for more than a decade. However, studies have shown that clozapine is more effective for refractory schizophrenia than other antipsychotics, the U.S. Food and Drug Administration and health authorities in most other countries approved its use only for refractory schizophrenia Patients require regular blood tests to monitor the neutrophil, and then agranuloctytosis development. December 2002, clozapine was also approved to reduce the risk of suicide in patients with schizophrenia or schizoaffective is considered in the risk of suicide.

Clozapine Uses

 Clozapine (CAS NO.5786-21-0) can be used as an antipsychotic.

Clozapine Production

 Clozapine (CAS NO.5786-21-0) can be obtained from the reaction of 2 - Amino -4 - chloro-aniline 2 -2 '- carboxylic acid (4''-methyl) piperazine with Phosphorus oxychloride .

Clozapine Toxicity Data With Reference

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
child TDLo oral 4762ug/kg (4.762mg/kg) BEHAVIORAL: ATAXIA
BEHAVIORAL: MUSCLE CONTRACTION OR SPASTICITY)
BEHAVIORAL: ANTIPSYCHOTIC		 American Journal of Emergency Medicine. Vol. 14, Pg. 462, 1996.
dog LD50 oral 145mg/kg (145mg/kg) GASTROINTESTINAL: NAUSEA OR VOMITING Farmaco, Edizione Pratica. Vol. 26, Pg. 585, 1971.
guinea pig LD50 oral 510mg/kg (510mg/kg)   Farmaco, Edizione Pratica. Vol. 26, Pg. 585, 1971.
human TDLo oral 5mg/kg/7D-I (5mg/kg) CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP Arzneimittel-Forschung. Drug Research. Vol. 22, Pg. 919, 1972.
man TDLo oral 4286ug/kg/11D (4.286mg/kg) GASTROINTESTINAL: "HYPERMOTILITY, DIARRHEA"
BLOOD: CHANGES IN CELL COUNT (UNSPECIFIED)		 Journal of Clinical Pyschopharmacology. Vol. 13, Pg. 155, 1993.
man TDLo oral 5357ug/kg/5D- (5.357mg/kg) BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS"
BEHAVIORAL: ANTIPSYCHOTIC
CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP		 Journal of Clinical Pyschopharmacology. Vol. 12, Pg. 139, 1992.
man TDLo oral 27mg/kg/13D-I (27mg/kg) AUTONOMIC NERVOUS SYSTEM: "SMOOTH MUSCLE RELAXANT (MECHANISM UNDEFINED, SPASMOLYTIC)"
BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS"
BEHAVIORAL: ATAXIA		 Journal of Clinical Psychiatry. Vol. 55, Pg. 38, 1994.
man TDLo oral 40mg/kg (40mg/kg) BEHAVIORAL: COMA

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION		 Veterinary and Human Toxicology. Vol. 41, Pg. 20, 1999.
man TDLo oral 86mg/kg/15D-I (86mg/kg) CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP
LUNGS, THORAX, OR RESPIRATION: OTHER CHANGES		 British Journal of Psychiatry. Vol. 173, Pg. 440, 1998.
man TDLo oral 270mg/kg/6W-I (270mg/kg) LUNGS, THORAX, OR RESPIRATION: STRUCTURAL OR FUNCTIONAL CHANGE IN TRACHEA OR BRONCHI
BLOOD: AGRANULOCYTOSIS
GASTROINTESTINAL: "HYPERMOTILITY, DIARRHEA"		 Annales de Medecine Interne. Vol. 144, Pg. 494, 1993.
man TDLo oral 429mg/kg/60D- (429mg/kg) BEHAVIORAL: MUSCLE CONTRACTION OR SPASTICITY) American Journal of Psychiatry. Vol. 152, Pg. 649, 1995.
man TDLo oral 429mg/kg (429mg/kg) BEHAVIORAL: MUSCLE CONTRACTION OR SPASTICITY)
CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP
BEHAVIORAL: COMA		 Journal of Toxicology, Clinical Toxicology. Vol. 38, Pg. 325, 2000.
man TDLo oral 2211mg/kg/37W (2211mg/kg) BLOOD: "CHANGES IN SERUM COMPOSITION (E.G., TP, BILIRUBIN, CHOLESTEROL)" Journal of Clinical Pyschopharmacology. Vol. 15, Pg. 287, 1995.
man TDLo oral 3280mg/kg/82W (3280mg/kg) BLOOD: AGRANULOCYTOSIS American Journal of Psychiatry. Vol. 153, Pg. 1503, 1996.
mouse LD50 intraperitoneal 90mg/kg (90mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD
BEHAVIORAL: MUSCLE CONTRACTION OR SPASTICITY)
LUNGS, THORAX, OR RESPIRATION: DYSPNEA		 Farmaco, Edizione Pratica. Vol. 26, Pg. 585, 1971.
mouse LD50 intravenous 36500ug/kg (36.5mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)
LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD		 Kiso to Rinsho. Clinical Report. Vol. 7, Pg. 667, 1973.
mouse LD50 oral 150mg/kg (150mg/kg)   Journal of Medicinal Chemistry. Vol. 23, Pg. 878, 1980.
mouse LD50 subcutaneous 194mg/kg (194mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)
BEHAVIORAL: EXCITEMENT
BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD		 Kiso to Rinsho. Clinical Report. Vol. 7, Pg. 667, 1973.
rat LD50 intramuscular 210mg/kg (210mg/kg)   Farmaco, Edizione Pratica. Vol. 26, Pg. 585, 1971.
rat LD50 intravenous 41600ug/kg (41.6mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD
LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION
BEHAVIORAL: ATAXIA		 Kiso to Rinsho. Clinical Report. Vol. 7, Pg. 667, 1973.
rat LD50 oral 251mg/kg (251mg/kg)   Kiso to Rinsho. Clinical Report. Vol. 7, Pg. 667, 1973.
rat LD50 subcutaneous 240mg/kg (240mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX)
BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD
LUNGS, THORAX, OR RESPIRATION: RESPIRATORY DEPRESSION		 Kiso to Rinsho. Clinical Report. Vol. 7, Pg. 667, 1973.
women TDLo oral 20mg/kg (20mg/kg) BEHAVIORAL: COMA
BLOOD: LEUKOPENIA
GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF ENDOCRINE PANCREAS		 Annals of Internal Medicine. Vol. 121, Pg. 722, 1994.
women TDLo oral 28mg/kg/2W-I (28mg/kg) GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF ENDOCRINE PANCREAS Lancet. Vol. 340, Pg. 251, 1992.
women TDLo oral 96mg/kg/48D-I (96mg/kg) BLOOD: LEUKOPENIA
BLOOD: AGRANULOCYTOSIS		 Human Psychopharmacology. Vol. 13, Pg. 583, 1998.
women TDLo oral 104mg/kg/26D- (104mg/kg) BLOOD: EOSINOPHILIA Journal of Clinical Psychiatry. Vol. 59, Pg. 195, 1998.
women TDLo oral 168mg/kg/4W-I (168mg/kg) BLOOD: AGRANULOCYTOSIS Netherlands Journal of Medicine. Vol. 52, Pg. 26, 1998.
women TDLo oral 280mg/kg/5W-I (280mg/kg) LIVER: "HEPATITIS (HEPATOCELLULAR NECROSIS), DIFFUSE"
BLOOD: EOSINOPHILIA		 American Journal of Psychiatry. Vol. 150, Pg. 985, 1993.

Clozapine Safety Profile

Hazard Codes: HarmfulXn,IrritantXi
Risk Statements: 22-36/37/38 
R22:Harmful if swallowed. 
R36/37/38:Irritating to eyes, respiratory system and skin.
Safety Statements: 26 
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.

Clozapine Specification

 Clozapine , its cas register number is 5786-21-0. It also can be called 8-Chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine ; Leponex ; and 5H-Dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)- . Many minor though some serious and potentially fatal: the more common include constipation, drooling, muscle stiffness, sedation, tremors, orthostasis, hyperglycemia, and weight gain. Extrapyramidal symptoms may subside somewhat after a person switches from another antipsychotic to Clozapine. Clozapine (CAS NO.5786-21-0) also carries black box warnings for seizures, myocarditis, and "other adverse cardiovascular and respiratory effects." Slow titration of dosing may also decrease the risk for orthostatic hypotension and other adverse cardiovascular side effects. It may have a synergistic effect with the sedating action of other drugs such as benzodiazepines, and thus respiratory depression may result with concomitant use. Care should be taken, especially if the latter drugs are given parenterally.

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