Blonanserin is used to treat schizophrenia in Japan and South Korea but not in the US.[6]
Adverse effects
As with many of the atypical antipsychotics, blonanserin can elicit cardio metabolic risks. While the side effects of blonanserin – such as weight gain, cholesterol and triglyceride levels, glucose levels and other blood lipid levels – do not differ greatly from other atypical antipsychotics, the specificity of blonanserin appears to elicit milder side effects, with less weight gain in particular.[5]
Blonanserin has a relatively high affinity towards the 5-HT6 receptor perhaps underpinning its recently unveiled efficacy in treating the cognitive symptoms of schizophrenia.[7][10] The efficacy of blonanserin can in part be attributed to its chemical structure, which is unique from those of other atypical antipsychotics.[11] Specifically, the addition of hydroxyl groups to blonanserin's unique eight membered ring results in the (R) stereoisomer of the compound demonstrating increased affinity for the indicated targets.[12]
* Towards human receptors unless otherwise specified.
Action at the Dopamine-D3 receptor
Blonanserin has antagonistic action at dopamine-D3 receptors that potentiates phosphorylation levels of Protein kinase A (PKA) and counteracts decreased activity at the dopamine-D1 and/or NMDA receptors, thus potentiating GABA induced Cl- currents.[9][13]Olanzapine does not appear to affect PKA activity.[9][14] Many antipsychotics, such as haloperidol, chlorpromazine, risperidone and olanzapine primarily antagonize serotonin 5-HT2A and dopamine-D2 receptors and lack known action at dopamine-D2/3 receptors.[9][11]
Blonanserin action at dopamine-D3 receptor. Cartoon of blonanserin's antagonistic impact at the dopamine-D3 receptor, reversing inhibition of PKA activity (also regulated by dopamine-D1 and NMDA activity) thus potentiating GABA induced Cl- current. Inset illustrates uninterrupted dopamine (DA) activity at the dopamine-D3 receptor. Inspired by Hida et al. (2014) and Yokota et al. (2002).[9][13]
Pharmacokinetics
Blonanserin is administered 4 mg orally twice a day or 8 mg once a day, for an adult male with a body mass index between 19–24 kg/m2 and a body weight equal to or greater than 50 kg.[15] The drug is absorbed by a two compartment (central and peripheral) model with first-order absorption and elimination.[1] The half-life of blonanserin is dependent on the dose. A single dose of 4 mg has a half-life of 7.7 ± 4.63 h and a single dose of 8 mg has a half-life of 11.9 ± 4.3 h.[15] The increase of half-life with dose is possibly attributed to there being more individual concentration per time points below the lower limit necessary for quantification in the lower single dose.[15]
Blonanserin is not a charged compound and exhibits very little chemical polarity. The polar surface area of Blonanserin is 19.7 Å[16] It is commonly accepted that a compound needs to have polar surface area less than 90 Å to cross the blood brain barrier so blonanserin is expected to be quite permeable as is demonstrated by a high brain/ plasma ratio of 3.88.[17]
Due to the good permeability of blonanserin, the volume of distribution in the central nervous system is greater than that in the periphery (Vd central = 9500 L, Vd periphery = 8650 L) although it is slower to absorb into the central compartment.[1]
Food intake slows the absorption of blonanserin and increases the bioavailability peripherally relative to centrally.[1] Single fasting doses are safe and the effects of feeding intake are possibly explained by an interaction between blonanserin and Cytochrome P450 3A4 in the gut.[15]
^ abcdefgWen YG, Shang DW, Xie HZ, Wang XP, Ni XJ, Zhang M, et al. (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. PMID23417765. S2CID12623938.
^Tenjin T, Miyamoto S, Miyake N, Ogino S, Kitajima R, Ojima K, et al. (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. PMID22278973. S2CID205925034. (Retracted, see doi:10.1002/hup.2622, PMID28657182, Retraction Watch. If this is an intentional citation to a retracted paper, please replace {{retracted|...}} with {{retracted|...|intentional=yes}}.)
^Ochi T, Sakamoto M, Minamida A, Suzuki K, Ueda T, Une T, et al. (February 2005). "Syntheses and properties of the major hydroxy metabolites in humans of blonanserin AD-5423, a novel antipsychotic agent". Bioorganic & Medicinal Chemistry Letters. 15 (4): 1055–1059. doi:10.1016/j.bmcl.2004.12.028. PMID15686911.
^Nagai T, Noda Y, Une T, Furukawa K, Furukawa H, Kan QM, Nabeshima T (February 2003). "Effect of AD-5423 on animal models of schizophrenia: phencyclidine-induced behavioral changes in mice". NeuroReport. 14 (2): 269–272. doi:10.1097/00001756-200302100-00023. PMID12598744. S2CID41717348.
^ abcdChen X, Wang H, Jiang J, Chen R, Zhou Y, Zhong W, et al. (March 2014). "The pharmacokinetic and safety profiles of blonanserin in healthy Chinese volunteers after single fasting doses and single and multiple postprandial doses". Clinical Drug Investigation. 34 (3): 213–222. doi:10.1007/s40261-013-0167-9. PMID24399453. S2CID35831132.
^ ab"Blonanserin". PubMed. U.S. National Library of Medicine.
^Tateno A, Arakawa R, Okumura M, Fukuta H, Honjo K, Ishihara K, et al. (April 2013). "Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia". Journal of Clinical Psychopharmacology. 33 (2): 162–169. doi:10.1097/jcp.0b013e3182825bce. PMID23422369. S2CID33775568.