ChemicalBook
Chinese Japanese Germany Korea

Clozapine

General description Pharmacological effects Pharmacodynamics Pharmacokinetics Uses Synthetic route Precautions Side effects Contraindications Chemical Properties Uses Production methods
Clozapine
Clozapine structure
CAS No.
5786-21-0
Chemical Name:
Clozapine
Synonyms
Iprox;W-801;Fazaclo;ozapine;Lepotex;LEPONEX;LIPONEX;HF-1854;Klozapol;clorazil
CBNumber:
CB7776111
Molecular Formula:
C18H19ClN4
Formula Weight:
326.82
MOL File:
5786-21-0.mol

Clozapine Properties

Melting point:
182-185°C
Boiling point:
482.71°C (rough estimate)
Density 
1.1327 (rough estimate)
refractive index 
1.6110 (estimate)
Flash point:
9℃
storage temp. 
Store at RT
solubility 
ethanol: 1 mg/mL
pka
3.70, 7.60(at 25℃)
form 
powder
color 
pale yellow
Merck 
14,2423
CAS DataBase Reference
5786-21-0(CAS DataBase Reference)
NIST Chemistry Reference
Clozapine(5786-21-0)
SAFETY
  • Risk and Safety Statements
  • Hazard and Precautionary Statements (GHS)
Hazard Codes  Xn,Xi,T,F
Risk Statements  22-36/37/38-68-63-39/23/24/25-23/24/25-11
Safety Statements  26-36/37-45-16-7
RIDADR  UN 2811 6.1/PG 3
WGK Germany  3
RTECS  HP1750000
HazardClass  6.1(b)
PackingGroup  III
HS Code  29339900
Hazardous Substances Data 5786-21-0(Hazardous Substances Data)
Toxicity LD50 in mice, rats (mg/kg): 61, 58 i.v.; 199, 260 orally (Lindt)
Symbol(GHS):
Signal word: Danger
Hazard statements:
Code Hazard statements Hazard class Category Signal word Pictogram P-Codes
H225 Highly Flammable liquid and vapour Flammable liquids Category 2 Danger P210,P233, P240, P241, P242, P243,P280, P303+ P361+P353, P370+P378,P403+P235, P501
H301 Toxic if swalloed Acute toxicity,oral Category 3 Danger P264, P270, P301+P310, P321, P330,P405, P501
H315 Causes skin irritation Skin corrosion/irritation Category 2 Warning P264, P280, P302+P352, P321,P332+P313, P362
H319 Causes serious eye irritation Serious eye damage/eye irritation Category 2A Warning P264, P280, P305+P351+P338,P337+P313P
H335 May cause respiratory irritation Specific target organ toxicity, single exposure;Respiratory tract irritation Category 3 Warning
H341 Suspected of causing genetic defects Germ cell mutagenicity Category 2 Warning P201,P202, P281, P308+P313, P405,P501
H361 Suspected of damaging fertility or the unborn child Reproductive toxicity Category 2 Warning P201, P202, P281, P308+P313, P405,P501
H370 Causes damage to organs Specific target organ toxicity, single exposure Category 1 Danger P260, P264, P270, P307+P311, P321,P405, P501
Precautionary statements:
P201 Obtain special instructions before use.
P210 Keep away from heat/sparks/open flames/hot surfaces. — No smoking.
P260 Do not breathe dust/fume/gas/mist/vapours/spray.
P261 Avoid breathing dust/fume/gas/mist/vapours/spray.
P264 Wash hands thoroughly after handling.
P264 Wash skin thouroughly after handling.
P270 Do not eat, drink or smoke when using this product.
P280 Wear protective gloves/protective clothing/eye protection/face protection.
P281 Use personal protective equipment as required.
P311 Call a POISON CENTER or doctor/physician.
P301+P310 IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P305+P351+P338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.
P405 Store locked up.
P501 Dispose of contents/container to..…

Clozapine price More Price(15)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich 1142107 Clozapine United States Pharmacopeia (USP) Reference Standard 5786-21-0 100mg $583 2018-11-13 Buy
Sigma-Aldrich 1142108 Clozapine Resolution Mixture United States Pharmacopeia (USP) Reference Standard 5786-21-0 30mg $1110 2018-11-13 Buy
TCI Chemical C2547 Clozapine >98.0%(GC)(T) 5786-21-0 1g $1032 2018-11-22 Buy
TCI Chemical C2547 Clozapine >98.0%(GC)(T) 5786-21-0 100mg $204 2018-11-22 Buy
Alfa Aesar J61583 Clozapine, 98+% 5786-21-0 100mg $329 2018-11-13 Buy

Clozapine Chemical Properties,Uses,Production

General description

Clozapine appears as pale yellow crystalline powder. It is odorless, tasteless with a molecular weight of 326.83 and a melting point 183~184 °C. It is soluble in chloroform, ethanol but insoluble in water. It is withdrawn from market because of causing neutropenia in 1976. Later studies have shown that this product has a good efficacy in treating schizophrenia, and thus had re-entered into market in 1989, 1990, in Sweden and the United States, respectively. This product is a non-classical antipsychotic which can selectively block DA receptors of the mesolimbic system but has a small effect on the nigrostriatal DA receptors. It has a relatively weak blocking effect on D2 receptor, but a strong blocking effect on D1 receptors strong while also has some antagonist effect on D4 receptor and 5-HT2 receptor. Thereby, it has strong anti-psychotic effects. Moreover EPS is less common and does not cause stiff reaction. Owing to the direct inhibition effect on the ascending reticular activating system of the brains, it has a potent sedative and hypnotic effects which can well applied for treating schizophrenia, hallucinations, delusions and youth-based effect. In addition to its good efficacy on treating positive symptoms like agitation, hallucinations, and paranoia, it also has a good efficacy on the negative symptoms. Since this product has a different mechanism of action on blocking DA receptors with traditional antipsychotics, thus this drug may also be effective in treating some classic antipsychotic disease which fails be treated with traditional drugs. It can also be used to alleviate mania and severe sleep disorders. In addition, it also has an anti-cholinergic effect. NE has sympathetic blocking effect, muscle relaxing effect and anti-histamine effect.

Pharmacological effects

1. Antipsychotic effects: Clozapine has good efficacy on treating various types of acute and chronic psychiatric disease. It can alleviate symptoms like excitement, agitation, hallucinations, delusion, thought disorder, depersonalization, and strange movements. The mechanism may be associated with its blocking effect on the dopamine receptor of mesolimbic system, but does not affect the dopamine receptors in the striatum, so this product rarely produces extrapyramidal reactions.
2. Sedative and hypnotic effects: This product can inhibit the spontaneous activity when applied in low-dose. High dose can increase automatic activity. Clozapine can directly inhibit the brain ascending reticular activating system.
3. Anti-cholinergic, anti-histamine and anti-adrenergic effects: The product has a strong anti-acetylcholine effect, and also has suppressing effect on histamine, norepinephrine and epinephrine.

Pharmacodynamics

This product is a kind of major tranquilizer which has well therapeutic effect on treating acute and chronic schizophrenia. Its mechanism of action is probably playing a pharmacological effect on central dopamine nerve. It can selectively block dopamine receptors in the limbic system with small effect on nigrostriatal dopamine receptor, so it has a strong anti-psychotic effect. The extrapyramidal side effects are rare. Its function also has no dependence on the activity of adenylate cyclase.

Pharmacokinetics

Its absorption through oral administration happens quickly and completely. There is no food effect on the rate and extent of absorption. It is widely distributed to various organizations after rapid absorption and there are large individual differences in bioavailability with an average deviation of about 50% to 60%. It also has hepatic first-pass effect. The plasma concentration reaches peak 3.2 hours (1-4 hours) after taking drugs and has an elimination half-life (t1/2β) about 9 hours. The apparent volume of distribution (Vd) is 4.04~13.78L/kg. It has a high tissue binding rate. After being metabolized by the liver, 80% of it is in the form of metabolites presented in urine and feces. Its major metabolites include N-demethylated clozapine, and the N-oxidant of clozapine. Under the same dose and a constant body weight, serum drug concentrations of female patients are significantly higher than that of male patients. Smoking can accelerate the metabolism of this product. Drug metabolism and renal clearance are significantly lower in the elderly. This product can be secreted from the milk, and can penetrate through the blood-brain barrier.
The above information is edited by the Chemicalbook of Dai Xiongfeng.

Uses

1. It is used for treating acute, chronic mania. It can be used to stabilize the emotion of human. It has good efficacy on treating symptoms like, vagrancy, sleep disorder, sadness, panic, tiredness, easy to be ill, sudden violence, and anger.
2. It can be used for treating crazy disease due to a variety of reasons such as losing temper, aggressive, emotional instability, anxiety, tension, and manic, etc.
3. It can be used for treating mental retardation-caused behavioral disorders such as linguistic disorder, poor presentation ability, poor thought and mental ability, lack of abstraction, generalization ability, low perception, narrow perception range, being difficult to distinguish small differences in body shape, size and color, lack of concentration, narrow attention range, poor memory, slow memorizing and reproducing inaccurately, na?ve behavior, immaturity, emotional instability, lack of self-control and impulsiveness, frequently being timid, withdrawn, shy, asymmetrical shape, uncoordinated movements, poor flexibility, performance, or hyperactivity, destruction, aggression.
4. It can be used for treating drug or alcohol-dependence withdrawal syndrome such as acute tremors, agitation, being easy to get startled, and nausea, vomiting and sweating. Upon drinking, the symptoms disappeared immediately, otherwise last for several days. There is sometimes even a short delusions, hallucinations and visual distortion, lisp. Finally, the patient may have seizures or delirium tremens.
5. Can be used for treating insomnia. It is applicable to the various manifestations of insomnia, such as dreaminess and being easy to wake up, heart palpitations, forgetfulness, and tiredness.

Synthetic route

Use 2,5-dichloro-nitrobenzene (2) and anthranilic acid (3) to react in DMF to generate 2-(4-chloro-2-nitro) dimethylbenzene (4), dimethylbenzene undergoes hydrazine hydrate/ferric chloride catalytic reduction to produce 2-(2-amino-4-chlorophenyl) dimethylbenzene (5), dimethylbenzene goes through cyclization reaction with the catalysis of polyphosphoric acid to obtain 8-chloro-5,10-dihydro-11H-dibenzo [b, e] [1,4]-dinitrogen-11-one (6). Product in step 6 is condensed together with N-methylpiperazine in the effect of titanium tetrachloride to get the final product.
the synthesis route of clozapine
Figure 1 the synthesis route of clozapine

Precautions

1. Induction of the decrease of neutropenia or its development into agranulocytosis is the most serious side effects of this product. So do not take drugs which causes leukopenia simultaneously while taking clozapine, especially avoid taking the traditional antipsychotic or antidepressant drugs or long-acting antipsychotics. Leukocyte count should be performed before treatment in order to understand the patient to return to normal polymorphonuclear leukocytes index. After the start of treatment, weekly leukocyte count should be performed for 18 consecutive weeks. Then the test should be done at least once a month. Do the same things during long-term medication. At each time of consultation, remind the patients to seek medical treatment immediately when infection or fever occurs. When there is an infection or WBC is less than 3.5 × 109/L or be much lower compared to the initial measured index, the white blood cell count should be reviewed immediately. If the absolute value of leukocyte reduced to 3 × 109/L or less and/or neutrophil polymorphonuclear leukocytes have an absolute value being less than 1.5 × 109/L, should be immediately discontinued.
2. For patients with a history of seizures or cardiovascular, renal, hepatic insufficiency, apply a lower initial dose and should increase the dose more gradually.
3. For patients with non-serious liver disease, clinical monitoring and regularly check of liver function is necessary.
4. Remind the patient that this product has the role of triggering drowsiness. So do not drive and operate machinery while taking the drug.
5. It has interaction with the central sedative and antipsychotic drugs, so be cautious when taking medicine.
6. Lactating women should not be breastfeeding upon medication.
7. Disable who are allergic to clozapine.
8. Patients with neutropenia, agranulocytosis or an apparent history of blood disease; Be cautious for patients of alcohol and drug-induced psychosis, poisoning and coma, severe heart, liver, kidney diseases, angle-closure glaucoma, and prostatic hypertrophy-caused urinary tract disease.

Side effects

Common adverse reactions include salivation (significantly during sleeping), nausea, vomiting, and abdominal distension. Occasionally fever, neutropenia, and a long-term drug addiction occur.

Contraindications

Children under 16 years of age, patients of angle-closure glaucoma, prostatic hyperplasia, spastic disorders or with a history of epilepsy and severe cardiovascular disease should take with caution. Disable it for patients with significantly inhibited central nervous system and with a history of myelosuppression or abnormal blood cells.

Chemical Properties

Light yellow crystalline powder with melting point 183-184 °C. It is easily soluble in chloroform, soluble in ethanol, almost insoluble in water. It is odorless, tasteless.

Uses

1. The product has not only a strong anti-psychotic effect, but also a calming effect as a novel broad-spectrum psychiatric drug which is suitable for treating acute and chronic schizophrenia. It has a good efficacy on treating paranoid hallucinations, youth-based diseases. In the angle of alleviating the symptoms, it is quite effective in treating agitation, hallucinations, delusions, contacts, and apastia.
2. Used as antipsychotics

Production methods

2-amino-4-chloro-diphenylamine-2'-carboxylic acid (4''-methyl) piperazine reacts with phosphorus oxychloride to get clozapine.

Chemical Properties

Yellow Crystalline Solid

Uses

An antipsychotic

Uses

depigmentor

Definition

ChEBI: A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatr c disorders like schizophrenia.

brand name

Clozaril (Novartis); Fazaclo (Avanir);Leponox.

World Health Organization (WHO)

Clozapine, a tricyclic neuroleptic, was introduced in 1972 for the treatment of psychosis. In 1975 its use was associated with cases of agranulocytosis, particularly in Finland. These cases, which included several fatalities, resulted in the withdrawal of the drug in some countries. However, clozapine remains available in at least 30 countries, in some cases only on special request, for the treatment of severe psychotic disorders unresponsive to other neuroleptics provided that close monitoring of the blood count is feasible. In 1989, it was introduced in the United States for the treatment of severe schizophrenia. Lately, the use of clozapine in the United Kingdom has been associated with convulsions. (Reference: (WHODIB) WHO Drug Information Bulletin, 2: 10, , 1977)

General Description

Clozapine, 8-chloro-11-(4-methyl-1-piperazinyl)5H-dibenzo[b,e] [1,4] diazepine (Clozaril), is a yellowcrystalline powder that is only slightly soluble in water. Withthe introduction of clozapine, a different pharmacological antipsychotics.106 Unlike typical antipsychotics, clozapine is largelydevoid of EPS. The lack of EPS with this compound waspostulated to be caused by its preferential binding tomesolimbic rather than striatal DA receptors.Furthermore,clozapine was shown to exhibit potent affinity for 5-HT2Areceptors.
DMCZ shows partial agonism at D2 and D3 receptors andexhibits a distinctly different pharmacological profile comparedwith clozapine and other atypical antipsychotics.Unlike clozapine, which is a potent M1 muscarinic antagonist,DMCZ is a potent M1 agonist. Agonism at muscarinicreceptors has been proposed to be useful for impaired cognitionin schizophrenia. Burnstein et al.found thatDMCZ acted as a partial agonist at DA D2 and D3 receptors.These investigators suggested that the low incidence of EPSassociated with clozapine may be caused by the partial agonismof DMCZ at D2 and D3 receptors. Thus, DMCZ maybe of interest as an atypical antipsychotic with an improvedside effect profile compared with clozapine.

General Description

The dibenzodiazepine derivative is clozapine(Clozaril). It is not a potent antipsychotic on a milligrambasis (note the orientation of the N-methyl piperazino grouprelative to the chlorine atom). In addition to their moderatepotencies at DA receptors (mainly D4), clozapine interactwith varying affinities at several other classes of receptors(α1 and α2 adrenergic, 5-HT1A, 5-HT2A, 5-HT2C, muscariniccholinergic, histamine H1, and others). It is effective againstboth positive and negative symptoms of schizophrenia andhas a low tendency to produce EPS. Clozapine has proved effectiveeven in chronically ill patients who respond poorly tostandard neuroleptics. However, there are legal restrictionson its use because of a relatively high frequency of agranulocytosis.As a rule, two other antipsychotics are tried beforerecourse to therapy with clozapine. Clozapine is metabolized preferentially by CYP3A4 into demethylated, hydroxylated,and N-oxide derivatives that are excreted in urine and feces.Elimination half-life averages about 12 hours. Other clozapine-like atypical antipsychotics may lack a 2-Cl substituenton the aromatic ring (e.g., olanzapine and quetiapine).

Biological Activity

Atypical antipsychotic drug, with a much lower tendency to cause extrapyramidal side effects than conventional neuroleptics. Displays a broad range of pharmacological actions; the antipsychotic effects are thought to be mediated principally by 5-HT 2A/2C and dopamine receptor blockade (K i values are 21, 170, 170, 230 and 330 nM for D 4 , D 3 , D 1 , D 2 and D 5 receptors respectively).

Clinical Use

Although clozapine demonstrates a favorable pharmacologicalprofile compared with typical antipsychotics, its useis restricted by a relatively high incidence of agranulocytosis.The exact mechanism for the cause of agranulocytosishas not been confirmed, but a highly reactive nitrenium ionthat is formed by the action of hepatic enzymes appears tobe involved.The mean elimination half-life of clozapine following a single 75-mg dose is 8 hours. Because of severaladverse effects, clozapine is only used in refractory casesof schizophrenia. Individuals with a history of seizures orpredisposed to seizures should be cautioned when takingclozapine. Similar to other atypical antipsychotic agents,clozapine causes an increased risk of mortality in elderly individualswith dementia-related psychoses.

Clozapine Preparation Products And Raw materials

Raw materials

Preparation Products


Clozapine Suppliers

Global( 265)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Capot Chemical Co.,Ltd.
+86 (0)571-855 867 18
+86 (0)571-858 647 95 sales@capotchem.com China 19918 60
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 20672 55
Mainchem Co., Ltd.
+86-0592-6210733
+86-0592-6210733 sales@mainchem.com CHINA 32447 55
Nanjing ChemLin Chemical Industry Co., Ltd.
025-83697070;product@chemlin.com.cn
product@chemlin.com.cn CHINA 3015 60
Hubei XinRunde Chemical Co., Ltd.
+8615102730682; +8618874586545
02783214688 bruce@xrdchem.cn CHINA 535 55
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 24192 60
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 27142 58
Chemwill Asia Co.,Ltd.
86-21-51086038
86-21-51861608 chemwill_asia@126.com;sales@chemwill.com;chemwill@hotmail.com;chemwill@gmail.com CHINA 23967 58
Hubei Jusheng Technology Co.,Ltd.
86-18871470254
027-59599243 sales@jushengtech.com CHINA 28236 58
QUALITY CONTROL CHEMICALS INC.
(323) 306-3136
(626) 453-0409 orders@qcchemical.com United States 8407 58

View Lastest Price from Clozapine manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2018-12-24 Clozapine
227-313-7
US $2.00 / kg 1kg 99% 100kg career henan chemical co
2018-08-20 Clozapine
5786-21-0
US $1.00 / KG 1G 98% 100KG career henan chemical co
2018-03-10 Dioxoprome
5786-21-0
US $100.00 / KG 10G 99% 10MT Hubei XinRunde Chemical Co., Ltd.

5786-21-0(Clozapine)Related Search:


Copyright 2017 © ChemicalBook. All rights reserved