Page last updated: 2024-10-15

clozapine n-oxide

Description

clozapine N-oxide: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID135445691
CHEMBL ID1688
CHEBI ID169893
SCHEMBL ID9014028
MeSH IDM0211955

Synonyms (46)

Synonym
CHEBI:169893
34233-69-7
3-chloro-6-(4-methyl-4-oxidopiperazin-4-ium-1-yl)-11h-benzo[b][1,4]benzodiazepine
clozapine-n-oxide
vufb-12426
5h-dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-, n-oxide
8-chloro-11-(4-methyl-1-piperazinyl)-5h-dibenzo(b,e)(1,4)diazepine n-oxide
CNO ,
clozapine n-oxide
CHEMBL1688 ,
AKOS005066164
FT-0665138
bdbm50279241
8-chloro-11-(4-methyl-1-piperazinyl)-5h-dibenzo[b,4]diazepine n-oxide
nsc-750266
nsc750266
5h-dibenzo[b,4]diazepine, 8-chloro-11-(4-methyl-1-piperazinyl)-, n-oxide
nsc 750266
mza8bk588j ,
unii-mza8bk588j
8-chloro-11-(4-methyl-1-piperazinyl)-5h-dibenzo[b,e](1,4)diazepine n-oxide
5h-dibenzo(b,e)(1,4)diazepine, 8-chloro-11-(4-methyl-4-oxido-1-piperazinyl)-
CS-1618
HY-17366
SCHEMBL9014028
c18h19cln4o
8-chloro-11-(4-methyl-4-oxido-1-piperazinyl)-5h-dibenzo[b,e][1,4]diazepine
5h-dibenzo[b,e][1,4]diazepine, 8-chloro-11-(4-methyl-4-oxido-1-piperazinyl)-
n-oxyclozapine
OGUCZBIQSYYWEF-UHFFFAOYSA-N
HB1807
clozapine n-oxide (cno) (freebase)
8-chloro-11-(4-methyl-4-oxido-1-pip erazinyl)-5h-dibenzo[b,e][1,4]diazepine
clozapine (n-oxide)
4-(8-chloro-5h-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylpiperazine 1-oxide
J-019512
(e)-4-(8-chloro-5h-dibenzo[b,e][1,4]diazepin-11-yl)-1-methylpiperazine 1-oxide
EX-A2353
BCP28618
W18756
Q27284305
DTXSID50955778
8-chloro-11-(4-methyl-4-oxo-4lambda~5~-piperazin-1-yl)-5h-dibenzo[b,e][1,4]diazepine
BC161997
clozapine n-oxide dihydrochloride- bio-x
BC162765

Pharmacokinetics

ExcerptReference
"The pharmacokinetic parameters of clozapine and its two main metabolites, N-desmethylclozapine (norclozapine, active metabolite) and clozapine N-oxide, were evaluated, after oral administration, in 19 patients with chronic schizophrenia."( Multiple-dose pharmacokinetics of clozapine in patients with chronic schizophrenia.
Abbar, M; Bressolle, F; Chabrand, P; Guitton, C; Kinowski, JM, 1998
)

Bioavailability

ExcerptReference
" To overcome these barriers, we created transgenic mice expressing an evolved G protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug clozapine-N-oxide (CNO)."( Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors.
Abbas, AI; Alexander, GM; Allen, JA; Armbruster, BN; Hartmann, J; McNamara, JO; Moy, SS; Nicolelis, MA; Nonneman, RJ; Pei, Y; Rogan, SC; Roth, BL, 2009
)
" hM4Di has no effect in the absence of its selective, normally inactive and orally bioavailable agonist clozapine-N-oxide (CNO)."( Chemical-genetic attenuation of focal neocortical seizures.
Kätzel, D; Kullmann, DM; Nicholson, E; Schorge, S; Walker, MC, 2014
)
" One reason for the slow adoption of DREADD technology in primates is that the pharmacokinetic properties and bioavailability of clozapine-n-oxide (CNO), the most commonly used ligand for human muscarinic (hM) DREADDs, are not fully described in primates."( Metabolism and Distribution of Clozapine-N-oxide: Implications for Nonhuman Primate Chemogenetics.
Bachevalier, J; Daniels, JS; Galvan, A; Howell, L; Morrison, RD; Raper, J; Wichmann, T, 2017
)

Dosage Studied

ExcerptReference
" In 25 patients at steady state at a mean daily clozapine dosage of 269 mg (3."( Determination of clozapine, norclozapine, and clozapine-N-oxide in serum by liquid chromatography.
Baldessarini, RJ; Centorrino, F; Flood, JG; Frankenburg, FR; Kando, J; Puopolo, PR; Volpicelli, SA, 1993
)
"8 yr) with treatment-resistant schizophrenia were treated with clozapine for 18 weeks; dosage was adjusted according to clinical response, and plasma concentrations of clozapine and of its metabolites were measured weekly by high-performance liquid chromatography."( Effectiveness of clozapine in neuroleptic-resistant schizophrenia: clinical response and plasma concentrations.
Auquier, P; Disdier, B; Farisse, J; Lancon, C; Llorca, PM; Sapin, C, 2002
)
"The mean endpoint clozapine dosage was 486."( Effectiveness of clozapine in neuroleptic-resistant schizophrenia: clinical response and plasma concentrations.
Auquier, P; Disdier, B; Farisse, J; Lancon, C; Llorca, PM; Sapin, C, 2002
)
" Monitoring plasma rates remains a useful tool, together with clinical evaluation, to establish the clozapine dosage for an optimum benefit-risk ratio."( Effectiveness of clozapine in neuroleptic-resistant schizophrenia: clinical response and plasma concentrations.
Auquier, P; Disdier, B; Farisse, J; Lancon, C; Llorca, PM; Sapin, C, 2002
)
" Lipid deposition in livers of patients with the metabolic syndrome may necessitate dosage adjustments for toxic drugs, including CLZ."( Impaired microsomal oxidation of the atypical antipsychotic agent clozapine in hepatic steatosis.
Murray, M; Ramzan, I; Zhang, WV, 2007
)
" In vivo assessment of CYP1A2 and CYP3A4 activities, perhaps by phenotyping approaches, could assist the optimization of CLZ dosage and minimize pharmacokinetic interactions with coadministered drugs."( Interindividual variation in relative CYP1A2/3A4 phenotype influences susceptibility of clozapine oxidation to cytochrome P450-specific inhibition in human hepatic microsomes.
D'Esposito, F; Edwards, RJ; Murray, M; Ramzan, I; Zhang, WV, 2008
)
" Therefore, abnormalities in the composition of gut microbiota by repeated dosing of DREADD ligands should be taken into consideration for behavioral and biological functions in rodents treated with DREADD ligands."( Abnormalities in the composition of the gut microbiota in mice after repeated administration of DREADD ligands.
Guo, W; Hashimoto, K; Ma, L; Wan, X; Zhang, J, 2021
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
dibenzodiazepineAny organic heterotricyclic compound with a skeleton consisting of two benzene rings fused to a diazepine ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)133.30000.00091.901410.0000AID397743
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (22)

Processvia Protein(s)Taxonomy
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (12)

Processvia Protein(s)Taxonomy
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (2)

Assay IDTitleYearJournalArticle
AID397743Inhibition of human ERG channel2009Journal of medicinal chemistry, Jul-23, Volume: 52, Issue:14
Side chain flexibilities in the human ether-a-go-go related gene potassium channel (hERG) together with matched-pair binding studies suggest a new binding mode for channel blockers.
AID1209886Drug level in pooled human liver microsomes treated with clozapine at 100 uM after 30 mins by HPLC analysis2013Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 41, Issue:3
Characterization of human cytochrome P450s involved in the bioactivation of clozapine.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (237)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's26 (10.97)18.2507
2000's22 (9.28)29.6817
2010's151 (63.71)24.3611
2020's38 (16.03)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials8 (3.32%)5.53%
Reviews3 (1.24%)6.00%
Case Studies1 (0.41%)4.05%
Observational0 (0.00%)0.25%
Other229 (95.02%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]