Blonanserin

Title: Blonanserin
CAS Registry Number: 132810-10-7
CAS Name: 2-(4-Ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine
Manufacturers' Codes: AD-5423
Trademarks: Lonasen (Dainippon)
Molecular Formula: C23H30FN3
Molecular Weight: 367.50
Percent Composition: C 75.17%, H 8.23%, F 5.17%, N 11.43%
Literature References: Dopamine D2 and serotonin 5-HT2 receptor antagonist. Prepn: K. Hino et al., EP 385237; eidem, US 5021421 (1990, 1991 both to Dainippon). HPLC determn in plasma: M. Matsuda et al., J. Pharm. Biomed. Anal. 15, 1449 (1997). X-ray crystal structure: K. Suzuki et al., Anal. Sci. 18, 1289 (2002). In vitro receptor binding study and in vivo pharmacology in animals: M. Oka et al., J. Pharmacol. Exp. Ther. 264, 158 (1993). Evaluation in mouse models of schizophrenia: T. Nagai et al., NeuroReport 14, 269 (2003). Review of development and clinical experience: C. E. Heading, Curr. Opin. Cent. Peripher. Nerv. Syst. Invest. Drugs 2, 79-84 (2002).
Properties: Crystals from acetonitrile, mp 123-124°.
Melting point: mp 123-124°
Therap-Cat: Antipsychotic.
Keywords: Antipsychotic; Serotonin-Dopamine Antagonist.
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Blonanserin
Blonanserin2D.svg
Blonanserin3Dan2.gif
Systematic (IUPAC) name
2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine
Clinical data
Trade names Lonasen
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 55% [1]
Metabolism CYP3A4[1]
Half-life 12 h[1]
Excretion 59% (urine), 30% (faeces)[1]
Identifiers
CAS number 132810-10-7
ATC code None
PubChem CID 125564
ChemSpider 111697
UNII AQ316B4F8C YesY
KEGG D01176
Chemical data
Formula C23H30FN3 
Mol. mass 367.50 g/mol

Blonanserin (Lonasen) is a relatively new atypical antipsychotic (approved by PMDA in January 2008)[2] commercialized by Dainippon Sumitomo Pharma in Japan and Korea for the treatment of schizophrenia.[3] Relative to many other antipsychotics, blonanserin has an improved tolerability profile, lacking side effects such as extrapyramidal symptoms, excessive sedation, or hypotension.[4] 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.[5]

Blonanserin acts as a mixed 5-HT2A (Ki = 0.812 nM) and D2 receptor (Ki = 0.142 nM) antagonist and also exerts some blockade of α1-adrenergic receptors (Ki = 26.7 nM).[6][7] It lacks significant affinity for numerous other sites including the 5-HT1A, 5-HT3, D1, α2-adrenergic, β-adrenergic, H1, and mACh receptors and the monoamine transporters,[7] though it does possess low affinity for the sigma receptor (IC50 = 286 nM).[7]

It has a relatively high affinity towards the 5-HT6 receptor perhaps underpinning its recently unveiled efficacy in treating the cognitive symptoms of schizophrenia.[6][8]

Receptor Ki [nM] (Blonanserin)* [6] Ki [nM] (N-deethylblonanserin)* [3]
D1 1070 1020
D2 0.142 1.38
D3 0.494 0.23
D4 150 -
D5 2600 -
5-HT1A 804 -
5-HT2A 0.812 1.28
5-HT2C 26.4 4.50
5-HT6 11.7 5.03
5-HT7 183 -
α1 26.7 (Rat brain) 206 (Rat receptor)
α2 530 (Rat cloned) -
M1 100 -
H1 765 -

* Towards human receptors unless otherwise specified.