Blonanserin

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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
ChEMBL CHEMBL178803
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.

See also[edit]

References[edit]

  1. ^ a b c d Wen, YG; Shang, DW; Xie, HZ; Wang, XP; Ni, XJ; Zhang, M; Lu, W; Qiu, C; Liu, X; Li, FF; Li, X; Luo, FT (March 2013). "Population pharmacokinetics of blonanserin in Chinese healthy volunteers and the effect of the food intake". Human Psychopharmacology 28 (2): 134–141. doi:10.1002/hup.2290. PMID 23417765. 
  2. ^ http://www.pmda.go.jp/english/service/pdf/list/NewdrugsFY2007.pdf
  3. ^ a b Deeks, ED; Keating, GM (January 2010). "Blonanserin A Review of its Use in the Management of Schizophrenia". CNS Drugs 24 (1): 65–84. doi:10.2165/11202620-000000000-00000. PMID 20030420. 
  4. ^ Heading CE (November 1998). "AD-5423 (Dainippon Pharmaceutical Co Ltd)". IDrugs : the Investigational Drugs Journal 1 (7): 813–7. PMID 18465651. 
  5. ^ Kishi T, Matsuda Y, Nakamura H, Iwata N. Blonanserin for schizophrenia: Systematic review and meta-analysis of double-blind, randomized, controlled trials. Journal of Psychiatric Research [Internet]. 2013 Feb [cited 2013 Aug 17];47(2) 149–54. Available from: http://www.sciencedirect.com/science/article/pii/S002239561200324X
  6. ^ a b c Tenjin, T; Miyamoto, S; Ninomiya, Y; Kitajima, R; Ogino, S; Miyake, N; Yamaguchi, N (2013). "Profile of blonanserin for the treatment of schizophrenia". Neuropsychiatric Disease and Treatment 9: 587–594. doi:10.2147/NDT.S34433. PMID 23766647. 
  7. ^ a b c Oka M, Noda Y, Ochi Y, et al. (January 1993). "Pharmacological profile of AD-5423, a novel antipsychotic with both potent dopamine-D2 and serotonin-S2 antagonist properties". The Journal of Pharmacology and Experimental Therapeutics 264 (1): 158–65. PMID 8093723. 
  8. ^ Tenjin, T; Miyamoto, S; Miyake, N; Ogino, S; Kitajima, R; Ojima, K; Arai, J; Teramoto, H; Tsukahara, S; Ito, Y; Tadokoro, M; Anai, K; Funamoto, Y; Kaneda, Y; Sumiyoshi, T; Yamaguchi, N (January 2012). "Effect of blonanserin on cognitive function in antipsychotic-naïve first-episode schizophrenia". Human Psychopharmacology 27 (1): 90–100. doi:10.1002/hup.1276. PMID 22278973.