Identification

Name
Blonanserin
Accession Number
DB09223
Type
Small Molecule
Groups
Investigational
Description

Blonanserin is an atypical antipsychotic approved in Japan in January, 2008. Relative to many other antipsychotics, blonanserin has an improved tolerability profile, lacking side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As with many second-generation (atypical) antipsychotics it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics such as haloperidol.

Structure
Thumb
Synonyms
Not Available
External IDs
AD 5423 / AD-5423
Categories
UNII
AQ316B4F8C
CAS number
132810-10-7
Weight
Average: 367.512
Monoisotopic: 367.242376141
Chemical Formula
C23H30FN3
InChI Key
XVGOZDAJGBALKS-UHFFFAOYSA-N
InChI
InChI=1S/C23H30FN3/c1-2-26-13-15-27(16-14-26)23-17-21(18-9-11-19(24)12-10-18)20-7-5-3-4-6-8-22(20)25-23/h9-12,17H,2-8,13-16H2,1H3
IUPAC Name
1-ethyl-4-[4-(4-fluorophenyl)-5H,6H,7H,8H,9H,10H-cycloocta[b]pyridin-2-yl]piperazine
SMILES
CCN1CCN(CC1)C1=NC2=C(CCCCCC2)C(=C1)C1=CC=C(F)C=C1

Pharmacology

Indication

Used for the treatment of schizophrenia [4].

Pharmacodynamics

Blonanserin antagonizes dopamine and serotonin receptors to reduce symptoms of schizophrenia [2].

Mechanism of action

Blonanserin binds to and inhibits dopamine receptors D2 and D3 as well as the serotonin receptor 5-HT2A with high affinity [2]. Blonanserin has low affinity for other dopamine and serotonin receptors as well as muscarinic, adrenergic, and histamine receptors. This reduces dopaminergic and serotonergic neurotransmission which is thought to produce a reduction in positive and negative symptoms of schizophrenia respectively.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
AD(3) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
Absorption

Blonanserin has a Tmax of 1.5 h and a bioavailablity of 55% [1, 2]. Tmax has been observed to be prolonged and relative bioavailability increased when administered with food [1].

Volume of distribution

Blonanserin has a Vc of 9500 L and a Vt of 8560 L for a total Vd of 18060 L [1].

Protein binding

Blonanserin is over 99.7% bound to plasma proteins [2] . Serum albumin is the primary binder.

Metabolism

Blonanserin is mainly metabolized by CYP3A4 [2]. It undergoes hydoxylation of the cyclooctane ring as well as N-oxidation and N-deethylation of the piperazine ring. The N-deethylated and hydroxylated metabolites are active but to a lesser degree than the parent drug.

Route of elimination

57% of blonanserin is excreted in the urine and 30% in the feces [2]. Only 5% of the drug in the feces is the parent drug with no parent drug excreted through the urine.

Half life

Blonanserin has a half life of elimination of 10.7-16.2 h [2].

Clearance

Blonanserin has a clearance of 1230 L/h [1].

Toxicity

Oral LD50 of >500 mg/kg in mice [5].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Blonanserin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Blonanserin is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Blonanserin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Blonanserin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Blonanserin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Blonanserin.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Blonanserin.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Blonanserin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Blonanserin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Blonanserin.
Food Interactions
Not Available

References

General References
  1. Wen YG, Shang DW, Xie HZ, Wang XP, Ni XJ, Zhang M, Lu W, Qiu C, Liu X, Li FF, Li X, Luo FT: Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake. Hum Psychopharmacol. 2013 Mar;28(2):134-41. doi: 10.1002/hup.2290. Epub 2013 Feb 18. [PubMed:23417765]
  2. Deeks ED, Keating GM: Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000. [PubMed:20030420]
  3. Zhou Y, Liu M, Jiang J, Wang H, Hu P: Simultaneous determination of blonanserin and its four metabolites in human plasma using ultra-performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 Nov 15;939:59-66. doi: 10.1016/j.jchromb.2013.09.007. Epub 2013 Sep 18. [PubMed:24099858]
  4. Blonanserin Approval Announcement [Link]
  5. ChemIDPlus: Blonanserin [Link]
External Links
KEGG Drug
D01176
PubChem Compound
125564
PubChem Substance
310265129
ChemSpider
111697
BindingDB
50160807
ChEBI
31296
ChEMBL
CHEMBL178803
Wikipedia
Blonanserin
MSDS
Download (42.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentSchizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP5.266MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0359 mg/mLALOGPS
logP5.76ALOGPS
logP5.67ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)7.97ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area19.37 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity111.05 m3·mol-1ChemAxon
Polarizability42.8 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001j-0961000000-b7df0ccb917e6467df2e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014j-0089000000-88be7b13b01a432d7bda

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyridinylpiperazines. These are compounds containing a pyridinylpiperazine skeleton, which consists of a pyridine linked (not fused) to a piperazine by a bond by a single bond that is not part of a ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Pyridinylpiperazines
Alternative Parents
Phenylpyridines / N-arylpiperazines / Dialkylarylamines / N-alkylpiperazines / Fluorobenzenes / Aminopyridines and derivatives / Imidolactams / Aryl fluorides / Heteroaromatic compounds / Trialkylamines
show 4 more
Substituents
4-phenylpyridine / Pyridinylpiperazine / N-arylpiperazine / Dialkylarylamine / Aminopyridine / Fluorobenzene / Halobenzene / N-alkylpiperazine / Aryl fluoride / Pyridine
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Deeks ED, Keating GM: Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000. [PubMed:20030420]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. Deeks ED, Keating GM: Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000. [PubMed:20030420]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Deeks ED, Keating GM: Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000. [PubMed:20030420]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Curator comments
Blonanserin appears to be a sensitive substrate with AUC increasing 13-16 fold with exposure to strong CYP3A4 inhibitors.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Deeks ED, Keating GM: Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000. [PubMed:20030420]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Deeks ED, Keating GM: Blonanserin: a review of its use in the management of schizophrenia. CNS Drugs. 2010 Jan;24(1):65-84. doi: 10.2165/11202620-000000000-00000. [PubMed:20030420]

Drug created on October 22, 2015 14:10 / Updated on November 02, 2018 07:00