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Clozapine 5-HT Receptor antagonist

Cat.No.S2459

Clozapine (HF 1854, LX 100-129) is an atypical antipsychotic drug by acting as a 5-HT antagonist, used in the treatment of schizophrenia.
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Quality Control

Batch: Purity: 99.99%
99.99

Solubility

In vitro
Batch:

DMSO : 65 mg/mL (198.88 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 65 mg/mL

Water : Insoluble

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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 326.82 Formula

C18H19ClN4

Storage (From the date of receipt)
CAS No. 5786-21-0 Download SDF Storage of Stock Solutions

Synonyms HF 1854, LX 100-129 SMILES CN1CCN(CC1)C2=NC3=C(C=CC(=C3)Cl)NC4=CC=CC=C42

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Mechanism of Action

Targets/IC50/Ki
5-HT2
In vitro
Clozapine (10, 20 mg/kg) significantly increases the number of Fos-positive neurons in the nucleus accumbens, medial prefrontal cortex and lateral septal nucleus. This compound induces zif268 but not c-fos mRNA in rat striatum, while Haloperidol induces c-Fos-like immunoreactivity in the caudate-putamen. It is more selective for D4 receptors compared to D2 receptors. This chemical is a mixed but weak D1/D2 antagonist. It produces a marked facilitation (300-400%) of NMDA-evoked responses in a concentration-dependent manner with EC50 of 14 nM. This compound, 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. It is a full agonist at the muscarinic M4 receptor (EC50 = 11 nM), producing inhibition of forskolin-stimulated cAMP accumulation. This chemical potently antagonizes agonist-induced responses at the other four muscarinic receptor subtypes.
In vivo
Clozapine 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. This compound decreases PPI independent of apomorphine treatment in the rats.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/9336328/
  • [5] https://pubmed.ncbi.nlm.nih.gov/7895765/
  • [6] https://pubmed.ncbi.nlm.nih.gov/1825226/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2026-07-31)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06969755 RECRUITING
Schizophenia Disorder
Northwell Health
2024-09-04 PHASE4
NCT05316883 RECRUITING
Schizophrenia; Psychosis
Jimmi Nielsen
2021-02-28 PHASE4
NCT07326124 NOT_YET_RECRUITING
Treatment Resistant Psychosis; Psychosis
University of Oxford
2026-06 PHASE3
NCT05208190 RECRUITING
Schizophrenia; Schizoaffective Disorder
New York State Psychiatric Institute
2022-03-17 PHASE4
NCT05603104 RECRUITING
Schizophrenia and Related Disorders; Major Depressive Disorder; Bipolar Depression
Dr. Inge Winter
2025-04-27 PHASE3
NCT05958875 RECRUITING
Schizophrenia and Related Disorders; Early Treatment-Resistance
Dr. Inge Winter
2024-08-01 PHASE4

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