Blonanserin (formerly AD 5423; AD-5423; AD5423) is an atypical antipsychotic agent acting as a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist with the potential to be used for the treatment of schizophrenia. Blonanserin has a better tolerability profile than many other antipsychotics because it doesn't cause side effects like hypotension, excessive sedation, or extrapyramidal symptoms. Blonanserin, like many other 2nd-generation (atypical) antipsychotics, is much more effective than haloperidol or other 1st-generation (typical) antipsychotics at treating the negative symptoms of schizophrenia.

Physicochemical Properties

Molecular Formula	C23H30FN3
Molecular Weight	367.5
Exact Mass	367.242
Elemental Analysis	C, 75.17; H, 8.23; F, 5.17; N, 11.43
CAS #	132810-10-7
Related CAS #	Blonanserin-d5; 1346599-86-7; Blonanserin dihydrochloride; 132812-45-4; Blonanserin-d8; 132812-47-6 (citrate)
PubChem CID	125564
Appearance	Solid powder
Density	1.1±0.1 g/cm3
Boiling Point	540.8±50.0 °C at 760 mmHg
Melting Point	117-119°C
Flash Point	280.9±30.1 °C
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.557
LogP	6.03
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	27
Complexity	443
Defined Atom Stereocenter Count	0
SMILES	FC1C([H])=C([H])C(=C([H])C=1[H])C1=C([H])C(=NC2C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C=21)N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1([H])[H]
InChi Key	XVGOZDAJGBALKS-UHFFFAOYSA-N
InChi Code	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
Chemical Name	2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine
Synonyms	AD 5423; AD-5423; AD5423
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	D2 Receptor ( Ki = 0.142 nM ); D3 Receptor ( Ki = 0.494 nM ); D4 Receptor ( Ki = 150 nM ); D1 Receptor ( Ki = 1070 nM ); 5-HT2A Receptor ( Ki = 0.812 nM ); 5-HT2C Receptor ( Ki = 26.4 nM ); 5-HT6 Receptor ( Ki = 11.7 nM ); α1-adrenergic receptor ( Ki = 26.7 ); α2-adrenergic receptor ( Ki = 530 )
ln Vitro	In vitro activity: Blonanserin exhibits considerable affinity for the D3 receptor (Ki=0.494 nM) and blocks some α1-adrenergic receptors (Ki=26.7 nM). Blonanserin has a low affinity for the sigma receptor (IC50=286 nM), but it is not very effective at many other sites, such as the monoamine transporters, 5-HT1A, 5-HT3, D1, α2-adrenergic, β-adrenergic, H1, and mACh receptors[1].
ln Vivo	Blonanserin (oral gavage; 1 mg/kg; 14 days) inhibits the decline in Ser897-phosphorylation levels and significantly improves the social deficit seen in mice given PCP; however, blonanserin treatment has no effect on the social behaviors of mice given saline[2].
Animal Protocol	Mice received saline or phencyclidine once a day for 14 consecutive days 1 mg/kg Oral gavage; 1 mg/kg; 14 days
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Blonanserin has a Tmax of 1.5 h and a bioavailablity of 55%. Tmax has been observed to be prolonged and relative bioavailability increased when administered with food. 57% of blonanserin is excreted in the urine and 30% in the feces. Only 5% of the drug in the feces is the parent drug with no parent drug excreted through the urine. Blonanserin has a Vc of 9500 L and a Vt of 8560 L for a total Vd of 18060 L. Blonanserin has a clearance of 1230 L/h. Metabolism / Metabolites Blonanserin is mainly metabolized by CYP3A4. 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. Biological Half-Life Blonanserin has a half life of elimination of 10.7-16.2 h.
Toxicity/Toxicokinetics	Protein Binding Blonanserin is over 99.7% bound to plasma proteins . Serum albumin is the primary binder.
References	[1]. Blonanserin. [2]. Blonanserin ameliorates social deficit through dopamine-D 3 receptor antagonism in mice administered phencyclidine as an animal model of schizophrenia. Neurochem Int. 2019 Sep;128:127-134.
Additional Infomation	Blonanserin is an organic molecular entity. Blonanserin is an atypical antipsychotic approved in Japan in January, 2008. It offers improved tolerability as it lacks side effects such as extrapyramidal symptoms, excessive sedation, or hypotension. As a second-generation (atypical) antipsychotic, it is significantly more efficacious in the treatment of the negative symptoms of schizophrenia compared to first-generation (typical) antipsychotics. Drug Indication Used for the treatment of schizophrenia. Mechanism of Action Blonanserin binds to and inhibits dopamine receptors D2 and D3 as well as the serotonin receptor 5-HT2A with high affinity. 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.

Solubility Data

Solubility (In Vitro)

DMSO: ~5 mg/mL (~13.6 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.43 mg/mL (3.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.43 mg/mL (3.89 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 1.43 mg/mL (3.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 14.3 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7211 mL	13.6054 mL	27.2109 mL
	5 mM	0.5442 mL	2.7211 mL	5.4422 mL
	10 mM	0.2721 mL	1.3605 mL	2.7211 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.