Clozapine (CED0001728)

Record Information

Version

1.0

Creation Date

2009-07-21 20:26:42 UTC

Update Date

2026-05-14 16:36:36 UTC

SynCED ID

CED0001728

Secondary Accession Numbers

CHEM002181
T3D2764

Identification

Common Name

Clozapine

Class

Small Molecule

Description

Clozapine belongs to the dibenzodiazepines, a subclass of benzodiazepines within the organic compounds. This exogenous organoheterocyclic compound has the formula C18H19ClN4 and an average molecular weight of 326.82 g/mol. At room temperature, it exists as a solid. It is found in healthcare, pharmaceuticals and veterinary products as an antipsychotic, and is also recorded in electrical and electronic equipment specifically in amplifiers. The recorded exposure route for this compound is oral. Clozapine is utilized as a second generation antipsychotic and functions as a biological application for several roles, acting as a serotonergic, dopaminergic, adrenergic, histamine, muscarinic, and GABA antagonist. Additionally, it serves as a chemical and biological inhibitor of EC 3.4.21.26 (prolyl oligopeptidase). The compound interacts with 35 recorded protein targets, including the D(4) dopamine receptor (DRD4), the D(2) dopamine receptor (DRD2), the Histamine H1 receptor (HRH1), and Neuron-specific vesicular protein calcyon (CALY). It also acts as an antagonist or positive modulator of Muscarinic acetylcholine receptors M2 (CHRM2), M3 (CHRM3), M4 (CHRM4), and M5 (CHRM5), among 14 other proteins. While the mechanism of action of Clozapine is unknown, it has been proposed that its therapeutic activity in schizophrenia is mediated through a combination of serotonin Type 2 (5HT2) and dopamine Type 2 (D2) receptor antagonism.

Contaminant Type

Amine
Antipsychotic Agent
Drug
GABA Antagonist
Human Neurotoxin
Metabolite
Organic Compound
Organochloride
Serotonin Antagonist
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Clozapin	ChEBI
Clozapina	ChEBI
Clozapinum	ChEBI
Clozaril	Kegg
Leponex	HMDB

Chemical Formula

C₁₈H₁₉ClN₄

Average Molecular Mass

326.823 g/mol

Monoisotopic Mass

326.130 g/mol

CAS Registry Number

5786-21-0

IUPAC Name

6-chloro-10-(4-methylpiperazin-1-yl)-2,9-diazatricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,9,11,13-heptaene

Traditional Name

clozapine

SMILES

CN1CCN(CC1)C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12

InChI Identifier

InChI=1S/C18H19ClN4/c1-22-8-10-23(11-9-22)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h2-7,12,20H,8-11H2,1H3

InChI Key

QZUDBNBUXVUHMW-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as dibenzodiazepines. Dibenzodiazepines are compounds containing a dibenzodiazepine moiety, which consists of two benzene connected by diazepine ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzodiazepines

Sub Class

Dibenzodiazepines

Direct Parent

Dibenzodiazepines

Alternative Parents

Substituents

Dibenzodiazepine
1,4-benzodiazepine
N-methylpiperazine
N-alkylpiperazine
Aryl chloride
Aryl halide
1,4-diazinane
Imidolactam
Piperazine
Benzenoid
Tertiary amine
Tertiary aliphatic amine
Amidine
Secondary amine
Organic 1,3-dipolar compound
Azacycle
Carboxylic acid amidine
Propargyl-type 1,3-dipolar organic compound
Organonitrogen compound
Organochloride
Organohalogen compound
Hydrocarbon derivative
Organopnictogen compound
Organic nitrogen compound
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

N-arylpiperazine (CHEBI:3766 )
organochlorine compound (CHEBI:3766 )
N-methylpiperazine (CHEBI:3766 )
benzodiazepine (CHEBI:3766 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Applications

Biological Roles

adrenergic antagonist ?
serotonergic antagonist ?
muscarinic antagonist (PMC10488274 )?
histamine antagonist ?
dopaminergic antagonist ?
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor ?
aryl hydrocarbon receptor agonist (PMC10488274 )?
agonist (PMC5756147 , PMC7925357 )?
GABA antagonist ?
antioxidant (PMC12347410 )?
drug (PMC8366481 , PMC13118352 )?
antipsychotic agent (PMC7456777 , PMC9304188 )?
second generation antipsychotic (PMC10190148 , PMC12264089 )?

Chemical Roles

EC 3.4.21.26 (prolyl oligopeptidase) inhibitor ?

Organoleptic Effects

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	183-184°C
Boiling Point	Not Available
Solubility	11.8 mg/L

Predicted Properties

Property	Value	Source
Water Solubility	0.19 g/L	ALOGPS
logP	3.67	ALOGPS
logP	3.4	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	15.9	ChemAxon
pKa (Strongest Basic)	7.35	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	30.87 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	97.36 m³·mol⁻¹	ChemAxon
Polarizability	35.77 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum	splash10-06r5-9064000000-0f31b1de88be42ac8381	Not Available	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum	Not Available	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00b9-0298000000-50d2ee0b52827fd1aee3	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-2690000000-daaa74a4f85f5e8b5926	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-bc2ca4d5a76a5facf897	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0009000000-986bc19f7e7e8602d005	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00b9-0049000000-d6315d4aeb74c251e939	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-27fd28450826291cc8c6	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0290000000-474b25ea27690471db0f	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0970000000-a58015260aaddb4245bd	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0930000000-3ccfd048a34fdb4f594f	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0009000000-7df53c42e3b1618bfdec	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0049000000-7522cc8ebf988effc792	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-bd138be4ae488c201ed3	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0190000000-68c8b78f304c38b7b7b5	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0980000000-a9dd724f32c02059c510	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0930000000-61c0f65f163824ddd594	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-da747a0572aa2c21683f	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-002f-0930000000-614883dbe075268cf23a	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00b9-0298000000-50d2ee0b52827fd1aee3	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-2690000000-daaa74a4f85f5e8b5926	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0009000000-6a5cb517440c1592abf6	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00b9-0049000000-91d037447eeb7ddec7f0	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0290000000-328730ac69c0a187556d	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-8b7f0b002676cde2b82e	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-5a9b3cf28962f0ee8a47	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0009000000-77845dce7dc9986039b2	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004i-0049000000-6381b0842b2c00cf838a	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-86dc1ea7be8412b9608c	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0920000000-7fbe9dedf784d23d08ab	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0920000000-342eb736c8147b04099e	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0970000000-61de277ac639907ae4a0	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0006-0960000000-925d09c355fc3be275a2	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0290000000-bbc7b75ce75e354f5b3c	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-00di-0090000000-a0ee4af55f94da3b26f2	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0009000000-b771968b218f574a2031	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-1049000000-24dab1e16fa5778e3f05	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-2190000000-6b669cd26b101d106f1c	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0009000000-178d40f752b4d092a8a6	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0029000000-5b7197f427b8cfdcdac2	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0006-4290000000-33f870d86d2adcc8f049	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0009000000-1fb75fb697641f932264	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0039000000-42c6b413e853bd1fe862	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00fu-0191000000-96b60ea49fe3e61ab787	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0009000000-4dd2a7daa08a9642d73b	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0059000000-1c82c8e60557dceb9924	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-0fc3-2090000000-e076d7de031202c4d9a7	Not Available	View Spectrum

Toxicity Profile

Toxicity Values

Toxicity Value	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Toxicity Rating	Reference
229.0 Log mg/kg [130:410]	Rat	LD50	oral	predicted	Not Available	Not Available

Toxicity / Toxin Class

Not Available

Mechanism of Toxicity

The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5HT₂) receptor antagonism. Atypical antipsychotic drugs such as clozapine have been proposed to block the 5HT2 and D2 receptors at therapeutic doses as evidenced by blockage in accelerating levels of growth hormone and cortisol secretion. The antipsychotic activity of clozapine is assumed to be the cause of D2 blockade while interacting with other receptors as well. With regards to mode of action in blocking dopaminergic receptors, clozapine exhibits higher affinity for D4 compared to the D2 receptor subtype. In addition, D1 antagonistic activity of clozapine enhances dopaminergic activity by increased extracellular brain dopamine concentrations specifically in the prefrontal cortex which is believed to explain its efficacy against negative symptoms generally observed in schizophrenia when using other drugs. Interestingly, clozapine has not been able to block arousal behavior which is the case when using other dopamine agonists after prolonged treatment. Interaction of clozapine with the immune system has also been found important when using this drug. Neutrophil apoptosis otherwise known as agranulocytosis was detected after administration of clopazine alone and bioactived clozapine to nitrenium ion at supratherapeutic and therapeutic levels, respectively. At supratherapeutic concentrations, clozapine can be toxic due to the drug itself or its stable metabolite products. At therapeutic levels however, the chemically reactive nitrenium ion is believed to bound to cellular protein, deplete intracellular GSH, and lead to final polymorphonuclear (PMN) and mononuclear leukocyte cytotoxicity in vitro. Agranulocytosis induced by bioactived clozapine can be inhibited by using antioxidants and genistein. PMN apoptosis is believed to be achieved by decelerating the life span of circulating cells after clozapine administration. Clozapine has also shown to interact with GABA receptors. Clozapine is able to induce release of glutamate and D-serine and decrease expression of glutamate transporters in astrocytic cell cultures with no neurons.

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Minimum Risk Level

Not Available

Symptoms

Not Available

Treatment

Establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. (13)

Health Effects

Health Effect	Relationship	Direction	Description	Reference
anemia	Associated With?	Not Available	A disorder characterized by a reduction in the amount of hemoglobin in 100 ml of blood. Signs and symptoms of anemia may include pallor of the skin and mucous membranes, shortness of breath, palpitations of the heart, soft systolic murmurs, lethargy, and fatigability. (NCI CTCAE)	PMC11505606 , PMC11505606
type 2 diabetes mellitus	Associated With?	increase	Not Available	PMC11505606
type 2 diabetes mellitus	Associated With?	Not Available	Not Available	PMC11505606 , PMC12733404
diabetes mellitus	Associated With?	Not Available	A glucose metabolism disease characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. (DO)	PMC11505606
diabetes mellitus	Associated With?	increase	A glucose metabolism disease characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. (DO)	PMC11505606
neutropenia	Associated With?	Not Available	A disorder characterized by an abnormally low level of neutrophils.	PMC12264089 , PMC10724599
weight gain	Associated With?	decrease	A finding characterized by an increase in overall body weight; for pediatrics, greater than the baseline growth curve. (NCI CTCAE)	PMC11505606
weight gain	Associated With?	Not Available	A finding characterized by an increase in overall body weight; for pediatrics, greater than the baseline growth curve. (NCI CTCAE)	PMC11505606
schizophrenia	Not Available	Not Available	A psychotic disorder that is characterized by a disintegration of thought processes and of emotional responsiveness. (DO)	PMC11505606 , PMC3622807
obesity	Associated With?	Not Available	A disorder characterized by having a high amount of body fat. (NCI CTCAE)	PMC7326440
seizure	Associated With?	Not Available	Not Available	PMC12264089 , PMC10724599
Toxic encephalopathy	Associated With?	Not Available	Not Available	PMC12473886
myocarditis	Associated With?	Not Available	A disorder characterized by inflammation of the muscle tissue of the heart. (NCI CTCAE)	PMC12264089
anxiety disorder	Not Available	Not Available	Not Available	PMC9143978
agranulocytosis	Associated With?	Not Available	Not Available	PMC11505606 , PMC12264089
agranulocytosis	Associated With?	decrease	Not Available	PMC5997408
agranulocytosis	Associated With?	increase	Not Available	PMC13118352
abdominal obesity-metabolic syndrome	Associated With?	Not Available	Not Available	PMC10724599
Abnormality of mitochondrial metabolism	Associated With?	decrease	Not Available	PMC13118352
Oxidative Stress	Associated With?	Not Available	Not Available	PMC12473886
Abdominal obesity	Associated With?	increase	Not Available	PMC11505606
depressive disorder	Not Available	Not Available	Not Available	PMC9143978
constipation disorder	Associated With?	Not Available	Not Available	PMC10724599
Cardiotoxicity	Associated With?	Not Available	Not Available	PMC10724599
hypotensive disorder	Associated With?	Not Available	Not Available	PMC10724599
hematopoietic system disease	Associated With?	Not Available	Not Available	PMC10724599
Immunosuppression Therapy	Associated With?	increase	Not Available	PMC11505606
Body Temperature	Associated With?	decrease	Not Available	PMC11505606
Schizophrenia, Treatment-Resistant	Not Available	Not Available	Not Available	PMC11505606 , PMC8366481
Impulsivity	Has Therapeutic Effect On	Not Available	Not Available	PMC4308438
Excessive salivation	Associated With?	Not Available	Not Available	PMC10724599
antisocial personality disorder	Not Available	Not Available	Not Available	PMC7456777
psychotic disorder	Not Available	Not Available	Not Available	PMC9143978 , PMC3429117
Central Nervous System Diseases	Not Available	Not Available	Not Available	PMC5748027
Mental Disorders	Not Available	Not Available	Not Available	PMC9943555
Mental Disorders	Associated With?	Not Available	Not Available	PMC9943555

Exposure Sources

Source ID	Source	Sector	Reference
CEDs000010	Insecticides?Insecticides are synthetic chemicals designed to control or eliminate insect pests that threaten crops and other agricultural products.	Agriculture & land management	PubChem
CEDs000013	Soil?Soil serves as a critical medium for plant growth and sustains various ecological functions; however, it can become a reservoir for synthetic chemical contamination.	Agriculture & land management	PMC12473886 , PMC12473886
CEDs000374	Antipsychotics?Antipsychotics are a class of synthetic chemicals used primarily for the treatment of psychiatric disorders, including schizophrenia and bipolar disorder.	Healthcare, pharmaceuticals & veterinary products	Not Available
CEDs000479	Effluent?Effluent refers to liquid waste or sewage that is discharged into the environment, typically resulting from industrial processes, municipal wastewater treatment, or agricultural runoff.	Wastewater, sanitation & biosolids	PMC9304188 , PMC9943555
CEDs000483	WWTP effluent?Wastewater treatment plant (WWTP) effluent can serve as a significant source of synthetic chemical contamination in the environment.	Wastewater, sanitation & biosolids	PMC9943555
CEDs000505	Amplifiers?Amplifiers, commonly used in various electronic devices to enhance signal strength, can be a source of synthetic chemical contamination due to the materials and processes involved in their production and disposal.	Electrical & Electronic Equipment	PubChem
CEDs000518	Electrically Stimulated Smoking Devices?Electrically stimulated smoking devices, commonly known as e-cigarettes or vape pens, utilize electrical components to heat a liquid solution, often containing nicotine, flavorings, and other additives, to produce an aerosol for inhalation.	Electrical & Electronic Equipment	PubChem
CEDs000530	Radio Transmission Systems?Radio transmission systems utilize a variety of synthetic chemicals in their manufacturing and maintenance processes.	Electrical & Electronic Equipment	PubChem
CEDs000545	Food Preservation?Food preservation often involves the use of synthetic chemicals, such as preservatives, flavor enhancers, and color additives, to extend shelf life and enhance the sensory qualities of food products.	Food, food processing & cookware	PubChem
CEDs000556	Cigar Cigarettes?Cigar cigarettes are a source of synthetic chemical contamination due to the combustion of various tobacco blends and additives.	Household cleaning & consumer products	PubChem
CEDs000559	Non Electric Simulated Smoking Devices?Non-electric simulated smoking devices, often designed to mimic the experience of smoking without combustion, can be sources of synthetic chemical contamination due to the materials and chemicals used in their construction and operation.	Household cleaning & consumer products	PubChem
CEDs000560	Other Smoking Requisites?Other smoking requisites, including items such as lighters, matches, and rolling papers, can introduce synthetic chemical contamination through various components and additives.	Household cleaning & consumer products	PubChem
CEDs000561	Perfumes Within Detergents And Soaps?Perfumes within detergents and soaps are synthetic fragrance compounds added to enhance the sensory experience of cleaning products.	Household cleaning & consumer products	PubChem
CEDs000569	Tobacco Smoke Filters?Tobacco smoke filters are designed to reduce the inhalation of harmful substances in cigarette smoke, including tar and other particulate matter.	Household cleaning & consumer products	PubChem
CEDs000580	Manufacture Preparation Of Tobacco Products?The manufacture and preparation of tobacco products involve various processes that can result in the introduction of synthetic chemicals into the environment.	Industrial manufacturing & chemical processing	PubChem
CEDs000596	Acaricides?Acaricides are synthetic chemicals specifically designed to target and control mite populations that can damage crops and plants.	Agriculture & land management	PubChem
CEDs000600	Herbicides And Algicides?Herbicides and algicides are synthetic chemicals primarily used to control unwanted plants and algae in various environments.	Agriculture & land management	PubChem
CEDs000610	Aftersun Products?Aftersun products are designed to soothe and hydrate the skin after sun exposure, often containing various synthetic chemicals such as emollients, preservatives, and fragrances.	Personal care & cosmetics	PubChem
CEDs000611	Anti Perspirants Or Body Deoderants?Antiperspirants and body deodorants commonly contain synthetic chemicals such as aluminum compounds, parabens, and synthetic fragrances.	Personal care & cosmetics	PubChem
CEDs000615	Eye Makeup Products?Eye makeup products, including mascaras, eyeliners, and eyeshadows, often contain a variety of synthetic chemicals such as pigments, preservatives, and film-forming agents.	Personal care & cosmetics	PubChem
CEDs000632	Apparel?Apparel production often involves the use of various synthetic chemicals, including dyes, finishing agents, and preservatives.	Textiles, leather & furnishings	PubChem
CEDs000642	Footwear?Footwear production often involves the use of various synthetic chemicals, such as adhesives, dyes, and treatments, which can contribute to environmental contamination.	Textiles, leather & furnishings	PubChem
CEDs000650	Purses Luggage Hand Bags?Purses, luggage, and handbags are often manufactured using synthetic materials such as polyvinyl chloride (PVC), polyurethane, and various types of nylon.	Textiles, leather & furnishings	PubChem
CEDs000671	Airplanes And Helicopters?Airplanes and helicopters are significant sources of synthetic chemical contamination primarily through the use of aviation fuels, lubricants, and de-icing agents.	Aviation & Aerospace	PubChem
CEDs000678	Nitrogenous Fertilisers?Nitrogenous fertilizers are synthetic chemical compounds primarily used to enhance plant growth by supplying essential nitrogen, a crucial nutrient for photosynthesis and protein synthesis.	Agriculture & land management	PubChem
CEDs000679	Phosphatic Fertilisers?Phosphatic fertilizers are synthetic chemical products primarily composed of phosphorus, which is essential for plant growth.	Agriculture & land management	PubChem
CEDs000685	Ceramics?Ceramics can be a source of synthetic chemical contamination through various additives and processing agents used in their production.	Building & Construction	PubChem
CEDs000693	Silica Glass?Silica glass, primarily composed of silicon dioxide (SiO2), is widely used in various applications, including windows, glass facades, and insulation materials.	Building & Construction	PubChem
CEDs000696	Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.	Industrial manufacturing & chemical processing	PubChem
CEDs000717	Fountain Pens?Fountain pens utilize a liquid ink that often contains synthetic chemicals, including dyes, pigments, and solvents, which can contribute to environmental contamination.	Paper, pulp & fiber products	PubChem
CEDs000720	Ink Reservoir Pens2?Ink reservoir pens are writing instruments that utilize a reservoir to store ink, which is often composed of synthetic dyes, solvents, and additives.	Paper, pulp & fiber products	PubChem
CEDs000730	Contact Lens Cases?Contact lens cases are small containers designed to store contact lenses in a sterile environment, typically made from various synthetic materials including plastics such as polypropylene or polycarbonate.	Healthcare, pharmaceuticals & veterinary products	PubChem
CEDs000734	Coating Compositions?Coating compositions, which include paints, sealants, and varnishes, are formulated with a variety of synthetic chemicals such as solvents, resins, pigments, and additives.	Building & Construction	PubChem
CEDs000735	Explosives?Explosives are chemical compounds or mixtures designed to undergo rapid decomposition, releasing energy in the form of gas and heat.	Defense & military infrastructure	PubChem
CEDs000739	Inks?Inks are complex mixtures composed of pigments or dyes, solvents, resins, and additives used primarily for printing and writing applications.	Paper, pulp & fiber products	PubChem
CEDs000741	Pigment Pastes?Pigment pastes are concentrated dispersions of pigments used to impart color and properties to materials.	Paper, pulp & fiber products	PubChem
CEDs000744	Water, Wastewater, & Sewage Treatment?Water, wastewater, and sewage treatment processes are critical for managing and mitigating pollutants in water systems.	Wastewater, sanitation & biosolids	PubChem
CEDs01425	Food Commodities	Food, food processing & cookware	PMC12473886
CEDs02293	Fresh Water	Aquatic systems & sediments	PMC12407060
CEDs02340	Water Body	Aquatic systems & sediments	PMC12473886
CEDs03009	Waste Water	Wastewater, sanitation & biosolids	PMC7456777
CEDs03061	WWTP	Wastewater, sanitation & biosolids	PMC9304188
CEDs03157	Municipal Effluent	Wastewater, sanitation & biosolids	PMC12407060

Pathways

7 pathwaysPathway Source: PathBank

Clozapine Serotonin Antagonist Action Pathway

Clozapine Dopamine Antagonist Action Pathway

Clozapine Drug Metabolism Action Pathway

Clozapine H1 Antihistamine Neurological Sleep Action Pathway

Clozapine H1 Antihistamine Smooth Muscle Relaxation Action Pathway

Clozapine H1-Antihistamine Blood Vessel Constriction Action Pathway

Clozapine H1-Antihistamine Immune Response Action Pathway

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	Mitogen-activated protein kinase	A3FQ79	Cryptosporidium parvum (strain Iowa II)	Known	Not Available
Click to view 3D structure	Catalase	P04040	Humans	Known	Not Available
Click to view 3D structure	Acetylcholinesterase	P22303	Humans	Known	Not Available
Click to view 3D structure	Heat shock 70 kDa protein 1A	P0DMV8	Humans	Known	Not Available
Click to view 3D structure	Muscarinic acetylcholine receptor M1	P11229	Humans	Predicted (SEA)	Prediction Confidence Score 0.736 Applicability Domain 1.0 Statistical Significance 6.00e-05 Supporting Reference Compounds 385 E-value 0.467095
Click to view 3D structure	D(2) dopamine receptor	P14416	Humans	Predicted (SEA)	Prediction Confidence Score 0.727 Applicability Domain 1.0 Statistical Significance 4.10e-04 Supporting Reference Compounds 1103 E-value 3.19182
Click to view 3D structure	5-hydroxytryptamine receptor 2A	P14842	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.708 Applicability Domain 1.0 Statistical Significance 1.90e-04 Supporting Reference Compounds 380 E-value 1.47914
Click to view 3D structure	5-hydroxytryptamine receptor 2C	P08909	Rat	Predicted (SEA)	Prediction Confidence Score 0.707 Applicability Domain 1.0 Statistical Significance 1.40e-04 Supporting Reference Compounds 185 E-value 1.08989
Click to view 3D structure	D(2) dopamine receptor	P61169	Rat	Predicted (SEA)	Prediction Confidence Score 0.7 Applicability Domain 1.0 Statistical Significance 4.00e-04 Supporting Reference Compounds 528 E-value 3.11397
Click to view 3D structure	D(1A) dopamine receptor	P18901	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.699 Applicability Domain 1.0 Statistical Significance 1.20e-04 Supporting Reference Compounds 206 E-value 0.934191
Click to view 3D structure	D(4) dopamine receptor	P21917	Humans	Predicted (SEA)	Prediction Confidence Score 0.686 Applicability Domain 1.0 Statistical Significance 2.80e-04 Supporting Reference Compounds 524 E-value 2.17978
Click to view 3D structure	Histamine H4 receptor	Q9H3N8	Humans	Predicted (SEA)	Prediction Confidence Score 0.655 Applicability Domain 1.0 Statistical Significance 7.00e-05 Supporting Reference Compounds 150 E-value 0.544945
Click to view 3D structure	D(1A) dopamine receptor	P21728	Humans	Predicted (SEA)	Prediction Confidence Score 0.655 Applicability Domain 1.0 Statistical Significance 4.10e-04 Supporting Reference Compounds 425 E-value 3.19182
Click to view 3D structure	D(3) dopamine receptor	P35462	Humans	Predicted (SEA)	Prediction Confidence Score 0.654 Applicability Domain 1.0 Statistical Significance 0.001 Supporting Reference Compounds 861 E-value 8.17417
Click to view 3D structure	Histamine H1 receptor	P31390	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.652 Applicability Domain 1.0 Statistical Significance 2.00e-05 Supporting Reference Compounds 63 E-value 0.155698
Click to view 3D structure	Muscarinic acetylcholine receptor M4	P08173	Humans	Predicted (SEA)	Prediction Confidence Score 0.638 Applicability Domain 1.0 Statistical Significance 1.30e-04 Supporting Reference Compounds 297 E-value 1.01204
Click to view 3D structure	Gap junction alpha-1 protein	P17302	Humans	Known	Not Available
Click to view 3D structure	Muscarinic acetylcholine receptor M2	P08172	Humans	Predicted (SEA)	Prediction Confidence Score 0.636 Applicability Domain 1.0 Statistical Significance 1.90e-04 Supporting Reference Compounds 373 E-value 1.47914
Click to view 3D structure	Muscarinic acetylcholine receptor M3	P20309	Humans	Predicted (SEA)	Prediction Confidence Score 0.636 Applicability Domain 1.0 Statistical Significance 2.30e-04 Supporting Reference Compounds 310 E-value 1.79053
Click to view 3D structure	Voltage-gated inwardly rectifying potassium channel KCNH2	Q12809	Humans	Predicted (SEA)	Prediction Confidence Score 0.635 Applicability Domain 1.0 Statistical Significance 7.40e-04 Supporting Reference Compounds 1498 E-value 5.76084
Click to view 3D structure	Muscarinic acetylcholine receptor M5	P08912	Humans	Predicted (SEA)	Prediction Confidence Score 0.617 Applicability Domain 1.0 Statistical Significance 1.50e-04 Supporting Reference Compounds 266 E-value 1.16774
Click to view 3D structure	5-hydroxytryptamine receptor 2A	P28223	Humans	Predicted (SEA)	Prediction Confidence Score 0.614 Applicability Domain 1.0 Statistical Significance 9.40e-04 Supporting Reference Compounds 955 E-value 7.31783
Click to view 3D structure	Alpha-2A adrenergic receptor	P08913	Humans	Predicted (SEA)	Prediction Confidence Score 0.581 Applicability Domain 1.0 Statistical Significance 5.70e-04 Supporting Reference Compounds 487 E-value 4.43741
Click to view 3D structure	5-hydroxytryptamine receptor 6	P50406	Humans	Predicted (SEA)	Prediction Confidence Score 0.576 Applicability Domain 1.0 Statistical Significance 6.50e-04 Supporting Reference Compounds 536 E-value 5.0602
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P08908	Humans	Predicted (SEA)	Prediction Confidence Score 0.561 Applicability Domain 1.0 Statistical Significance 0.0032 Supporting Reference Compounds 953 E-value 24.9118
Click to view 3D structure	Histamine H1 receptor	P35367	Humans	Predicted (SEA)	Prediction Confidence Score 0.546 Applicability Domain 1.0 Statistical Significance 0.0012 Supporting Reference Compounds 507 E-value 9.26406
Click to view 3D structure	5-hydroxytryptamine receptor 2C	P28335	Humans	Predicted (SEA)	Prediction Confidence Score 0.532 Applicability Domain 1.0 Statistical Significance 0.0022 Supporting Reference Compounds 823 E-value 17.5161
Click to view 3D structure	Sodium-dependent serotonin transporter	P31645	Humans	Predicted (SEA)	Prediction Confidence Score 0.53 Applicability Domain 1.0 Statistical Significance 0.0017 Supporting Reference Compounds 593 E-value 13.3901
Click to view 3D structure	Alpha-2B adrenergic receptor	P18089	Humans	Predicted (SEA)	Prediction Confidence Score 0.53 Applicability Domain 1.0 Statistical Significance 5.40e-04 Supporting Reference Compounds 340 E-value 4.20386
Click to view 3D structure	Alpha-2C adrenergic receptor	P18825	Humans	Predicted (SEA)	Prediction Confidence Score 0.53 Applicability Domain 1.0 Statistical Significance 6.40e-04 Supporting Reference Compounds 386 E-value 4.98235
Click to view 3D structure	Cytochrome P450 1A2	P05177	Humans	Known	Not Available
Click to view 3D structure	Dynamin-2	P50570	Humans	Known	Not Available
Click to view 3D structure	Dynamin-1	Q05193	Humans	Known	Not Available
Click to view 3D structure	D(2) dopamine receptor	P14416	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	D(4) dopamine receptor	P21917	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	5-hydroxytryptamine receptor 2A	P28223	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P08908	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	Voltage-gated inwardly rectifying potassium channel KCNH2	Q12809	Humans	Known	Not Available
Click to view 3D structure	5-hydroxytryptamine receptor 2C	P28335	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	Histamine H1 receptor	P35367	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	Histamine H4 receptor	Q9H3N8	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	D(1A) dopamine receptor	P21728	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	Muscarinic acetylcholine receptor M1	P11229	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	5-hydroxytryptamine receptor 1B	P28222	Humans	Known	Not Available
Click to view 3D structure	5-hydroxytryptamine receptor 1D	P28221	Humans	Known	Not Available
Click to view 3D structure	5-hydroxytryptamine receptor 1E	P28566	Humans	Known	Not Available
Click to view 3D structure	5-hydroxytryptamine receptor 3A	P46098	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	5-hydroxytryptamine receptor 6	P50406	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	5-hydroxytryptamine receptor 7	P34969	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	Adenosine receptor A3	P0DMS8	Humans	Known	Not Available
Click to view 3D structure	Alpha-1B adrenergic receptor	P35368	Humans	Known	Not Available
Click to view 3D structure	Alpha-2B adrenergic receptor	P18089	Humans	Known	Not Available
Click to view 3D structure	Alpha-2C adrenergic receptor	P18825	Humans	Known	Not Available
Click to view 3D structure	D(3) dopamine receptor	P35462	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	Muscarinic acetylcholine receptor M2	P08172	Humans	Known	Not Available
Click to view 3D structure	Muscarinic acetylcholine receptor M3	P20309	Humans	Known	Not Available
Click to view 3D structure	Muscarinic acetylcholine receptor M4	P08173	Humans	Known	Not Available
Click to view 3D structure	Muscarinic acetylcholine receptor M5	P08912	Humans	Known	Not Available
Click to view 3D structure	Neuron-specific vesicular protein calcyon	Q9NYX4	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT₂) receptor antagonism.
Click to view 3D structure	Alpha-1A adrenergic receptor	P35348	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	Alpha-2A adrenergic receptor	P08913	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.
Click to view 3D structure	D(1B) dopamine receptor	P21918	Humans	Known	The mechanism of action of Clozapine, as with other drugs used to treat schizophrenia, is unknown. However, it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of dopamine Type 2 (D2) and serotonin Type 2 (5HT2) receptor antagonism.

Concentrations

Not Available

External Links

DrugBank ID

DB00363

HMDB ID

HMDB0014507

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Clozapine

Chemspider ID

10442628

ChEBI ID

3766

PubChem Compound ID

Not Available

Kegg Compound ID

C06924

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Schmutz, J. and Hunziker, F.; US. Patent 3,539,573; November 10, 1970 .

MSDS

Not Available

General References

Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [PubMed: 11873706]
Alvir JM, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA: Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med. 1993 Jul 15;329(3):162-7. [PubMed: 8515788]
Vaddadi KS, Soosai E, Vaddadi G: Low blood selenium concentrations in schizophrenic patients on clozapine. Br J Clin Pharmacol. 2003 Mar;55(3):307-9. [PubMed: 12630982]
Naheed M, Green B: Focus on clozapine. Curr Med Res Opin. 2001;17(3):223-9. [PubMed: 11900316]
Lane HY, Chang YC, Chang WH, Lin SK, Tseng YT, Jann MW: Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999 Jan;60(1):36-40. [PubMed: 10074876]
Brunello N, Masotto C, Steardo L, Markstein R, Racagni G, New insights into the biology of schizophrenia through the mechanism of action of clozapine, Neuropsychopharmacology, 1995;13(3):177–213. [PubMed: 8602893]
Baldessarini RJ, Frankenburg FR, Clozapine – A novel antipsychotic agent, The new England journal of medicine, 1991;324(11):746-54. [PubMed: 1671793]
Meltzer, H. Y., Clinical studies on the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia, Psychopharmacology, 1989;99:S18-S27. [PubMed: 2682729]
Tanahashi S, Yamamura S, Nakagawa M, Motomura E, Okada M, Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release in rat frontal cortex and primary cultured astrocytes, Br J Pharmacol, 2012;165(5):1543-55. [PubMed: 21880034]
Williams DP, Pirmohamed M, Naisbitt DJ, Uetrecht JP, Park BK, Induction of Metabolism-Dependent and –Independent Neutrophil Apoptosis by Clozapine, Molecular Pharmacology, 2000;58:207–216. [PubMed: 10860943]
Wu Y, Blichowski M, Daskalakis ZJ, Wu Z, Liu CC, Cortez MA, Snead OC 3rd, Evidence that clozapine directly interacts on the GABAb receptor, Neuroreport, 2011;22(13):637-641. [PubMed: 21753741]
Drugs.com - http://www.drugs.com/cons/Clozapine.html
RxList: The Internet Drug Index (2009). - http://www.rxlist.com/

Clozapine (CED0001728)

Structure for CHEM002181: Clozapine

Structure