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    Clozapine (HF 1854)
    Clozapine (HF 1854)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0962
    CAS #: 5786-21-0Purity ≥98%

    Description: Clozapine (LX 100129; HF1854, LX100129; Leponex; Fazaclo; CLOZARIL; Clozapin; Clozaril) is an atypical antipsychotic drug wand a 5-HT antagonist used in the treatment of schizophrenia. It binds to serotonin and dopamine receptors. Clozapine is a partial agonist at the 5-HT1A subunit of the serotonin receptor, putatively improving depression, anxiety, and the negative cognitive symptoms associated with schizophrenia. A direct interaction of clozapine with the GABAB receptor has also been shown. GABAB receptor-deficient mice exhibit increased extracellular dopamine levels and altered locomotor behaviour equivalent to that in schizophrenia animal models. 

    References: Neuroscience. 1992;46(2):315-28; Proc Natl Acad Sci U S A. 1992 May 15;89(10):4270-4.

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    Molecular Weight (MW)326.82
    FormulaC18H19ClN4
    CAS No.5786-21-0
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 65 mg/mL (198.9 mM)
    Water: <1 mg/mL
    Ethanol: 32 mg/mL (97.9 mM)
    SMILES CodeCN1CCN(CC1)C2=C3C=CC=CC3=NC4=C(N2)C=C(C=C4)Cl
    SynonymsHF-1854, LX 100-129; HF 1854, LX 100129; HF1854, LX100129; Leponex; Fazaclo; CLOZARIL; Clozapin; Clozaril.


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    In Vitro

    In vitro activity: Clozapine (10, 20 mg/kg) significantly increases the number of Fos-positive neurons in the nucleus accumbens, medial prefrontal cortex and lateral septal nucleus. Clozapine induces zif268 but not c-fos mRNA in rat striatum, while Haloperidol induces c-Fos-like immunoreactivity in the caudate-putamen. Clozapine is more selective for D4 receptors compared to D2 receptors. Clozapine is a mixed but weak D1/D2 antagonist. Clozapine produces a marked facilitation (300-400%) of NMDA-evoked responses in a concentration-dependent manner with EC50 of 14 nM. Clozapine, but not haloperidol, produces bursts of excitatory postsynaptic potentials (EPSPs), which are blocked by glutamate receptor antagonists, suggesting that these EPSPs are the result of increasing release of excitatory amino acids. Clozapine is a full agonist at the muscarinic M4 receptor (EC50 = 11 nM), producing inhibition of forskolin-stimulated cAMP accumulation. Clozapine potently antagonizes agonist-induced responses at the other four muscarinic receptor subtypes.

    In VivoClozapine exhibits an 'inverted-U' shaped dose-response curve, reversing the apomorphine-induced loss of prepulse inhibition (PPI) at low doses but not at high doses in the rats. Clozapine decreases PPI independent of apomorphine treatment in the rats.
    Animal modelMice: 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
    Formulation & Dosage25 mg/kg
    References

    J Pharmacol Exp Ther. 1991 Feb;256(2):530-6; Neuroscience. 1992;46(2):315-28; Proc Natl Acad Sci U S A. 1992 May 15;89(10):4270-4; Psychopharmacology (Berl). 2013 Jan;225(1):217-26.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

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