Clozapine

Modify Date: 2024-01-02 12:02:39

Clozapine structure	Common Name	Clozapine
	CAS Number	5786-21-0	Molecular Weight	326.823
	Density	1.3±0.1 g/cm3	Boiling Point	489.2±55.0 °C at 760 mmHg
	Molecular Formula	C18H19ClN4	Melting Point	182-185°C
	MSDS	ChineseUSA	Flash Point	249.6±31.5 °C
	Symbol	GHS06, GHS08	Signal Word	Danger

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Use of Clozapine Clozapine (HF 1854) is an antipsychotic used to treat schizophrenia. Clozapine is a potent antagonist of dopamine and a number of other receptors, with a Ki of 9.5 nM for M1 receptor.

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 Names

Name	clozapine
Synonym	More Synonyms

 Clozapine Biological Activity

Description	Clozapine (HF 1854) is an antipsychotic used to treat schizophrenia. Clozapine is a potent antagonist of dopamine and a number of other receptors, with a Ki of 9.5 nM for M1 receptor.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor Research Areas >> Neurological Disease
Target	Ki: 9.5 nM (M1), 51 nM (α2-adrenoceptor), 75 nM (D2)[1]
In Vitro	Clozapine shows the unique property of having antipsychotic action but no Parkinson-like motor side effects. The chemical structure of clozapine facilitates a relatively rapid dissociation from D2 receptors. After short-term occupation of D2 receptors, peak neural activity raises synaptic dopamine, which then displaces clozapine. While clozapine also occupies other types of receptors, they may not have a significant role in preventing parkinsonism. Clozapine is very potent at D2 receptor with a Ki of 75 nM. Clozapine is also potent at the α2-adrenoceptor with a Ki value of 51 nM[1]. Clozapine causes paradoxical downregulation of 5-HT2A receptors. Clozapine also binds to 5-HT6 and 5-HT7 receptors with high affnity[2].
In Vivo	Head-twitch response is decreased and [3H]ketanserin binding is downregulated in 1, 7, and 14 days after chronic clozapine. 5-HT2A mRNA is reduced 1 day after chronic clozapine. Induction of c-fos, but not egr-1 and egr-2, is rescued 7 days after chronicclozapine[3].
Animal Admin	Mice: Mice are treated chronically (21 days) with 25 mg/kg/day clozapine. Experiments are conducted 1, 7, 14, and 21 days after the last clozapine administration. [3H]Ketanserin binding and 5-HT2A mRNA expression are determined in mouse somatosensory cortex. Head-twitch behavior, expression of c-fos, which is induced by all 5-HT2A agonists, and expression of egr-1 and egr-2, which are LSD-like specific, are assayed[3].
References	[1]. Seeman P, et al. Clozapine, a fast-off-D2 antipsychotic. ACS Chem Neurosci. 2014 Jan 15;5(1):24-9. [2]. Zhukovskaya NL, et al. Clozapine downregulates 5-hydroxytryptamine6 (5-HT6) and upregulates 5-HT7 receptors in HeLa cells. Neurosci Lett. 2000 Jul 21;288(3):236-40. [3]. Moreno JL, et al. Persistent effects of chronic clozapine on the cellular and behavioral responses to LSD in mice. Psychopharmacology (Berl). 2013 Jan;225(1):217-26.

 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

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