Synonym
Iloperidone, Fanapt, HP-873, iloperidone, Zomaril
IUPAC/Chemical Name
1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanone
InChi Key
XMXHEBAFVSFQEX-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H27FN2O4/c1-16(28)18-4-7-21(23(14-18)29-2)30-13-3-10-27-11-8-17(9-12-27)24-20-6-5-19(25)15-22(20)31-26-24/h4-7,14-15,17H,3,8-13H2,1-2H3
SMILES Code
CC(C1=CC=C(OCCCN2CCC(C3=NOC4=CC(F)=CC=C34)CC2)C(OC)=C1)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Iloperidone (HP 873) is a D2/5-HT2 receptor antagonist.
In vitro activity:
Iloperidone exerted a strong inhibitory effect on the activity of CYP3A4 (Ki = 0.38 and 0.3 µM in liver microsomes and supersomes, respectively) and CYP2D6 (Ki = 2.9 and 10 µM in liver microsomes and supersomes, respectively). Moreover, iloperidone attenuated the activity of CYP2C19 (Ki = 6.5 and 32 µM in liver microsomes and supersomes, respectively) and CYP1A2 (Ki = 45 and 31 µM in liver microsomes and supersomes, respectively).
Reference: Pharmacol Rep. 2020 Dec;72(6):1685-1694. https://pubmed.ncbi.nlm.nih.gov/32279279/
In vivo activity:
In conclusion, by affecting CYP2D activity in the brain, iloperidone may modify its pharmacological effect, via influencing the rate of dopamine and serotonin synthesis or the metabolism of neurosteroids. By elevating the CYP2D expression/activity in the substantia nigra and striatum (i.e., in the dopaminergic nigrostriatal pathway), iloperidone may attenuate extrapyramidal symptoms, while by decreasing the CYP2D activity and metabolism of neurosteroiods in the frontal cortex and cerebellum, iloperidone can have beneficial effects in the treatment of schizophrenia. In the liver, pharmacokinetic interactions involving chronic iloperidone and CYP2D substrates are likely to occur.
Reference: Cells. 2021 Dec 9;10(12):3472. https://pubmed.ncbi.nlm.nih.gov/34943983/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
38.5 |
90.27 |
| Ethanol |
4.0 |
9.38 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
426.48
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Thériault RK, St-Denis M, Hewitt T, Khokhar JY, Lalonde J, Perreault ML. Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia. Int J Mol Sci. 2021 May 24;22(11):5511. doi: 10.3390/ijms22115511. PMID: 34073710; PMCID: PMC8197248.
2. Danek PJ, Wójcikowski J, Daniel WA. The atypical neuroleptics iloperidone and lurasidone inhibit human cytochrome P450 enzymes in vitro. Evaluation of potential metabolic interactions. Pharmacol Rep. 2020 Dec;72(6):1685-1694. doi: 10.1007/s43440-020-00102-5. Epub 2020 Apr 11. PMID: 32279279; PMCID: PMC7704495.
3. Danek PJ, Daniel WA. Long-Term Treatment with Atypical Antipsychotic Iloperidone Modulates Cytochrome P450 2D (CYP2D) Expression and Activity in the Liver and Brain via Different Mechanisms. Cells. 2021 Dec 9;10(12):3472. doi: 10.3390/cells10123472. PMID: 34943983; PMCID: PMC8700221.
4. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. doi: 10.1016/s0014-2999(96)00840-0. PMID: 8997630.
In vitro protocol:
1. Thériault RK, St-Denis M, Hewitt T, Khokhar JY, Lalonde J, Perreault ML. Sex-Specific Cannabidiol- and Iloperidone-Induced Neuronal Activity Changes in an In Vitro MAM Model System of Schizophrenia. Int J Mol Sci. 2021 May 24;22(11):5511. doi: 10.3390/ijms22115511. PMID: 34073710; PMCID: PMC8197248.
2. Danek PJ, Wójcikowski J, Daniel WA. The atypical neuroleptics iloperidone and lurasidone inhibit human cytochrome P450 enzymes in vitro. Evaluation of potential metabolic interactions. Pharmacol Rep. 2020 Dec;72(6):1685-1694. doi: 10.1007/s43440-020-00102-5. Epub 2020 Apr 11. PMID: 32279279; PMCID: PMC7704495.
In vivo protocol:
1. Danek PJ, Daniel WA. Long-Term Treatment with Atypical Antipsychotic Iloperidone Modulates Cytochrome P450 2D (CYP2D) Expression and Activity in the Liver and Brain via Different Mechanisms. Cells. 2021 Dec 9;10(12):3472. doi: 10.3390/cells10123472. PMID: 34943983; PMCID: PMC8700221.
2. Kongsamut S, Roehr JE, Cai J, Hartman HB, Weissensee P, Kerman LL, Tang L, Sandrasagra A. Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol. 1996 Dec 19;317(2-3):417-23. doi: 10.1016/s0014-2999(96)00840-0. PMID: 8997630.
1: Dargani NV, Malhotra AK. Safety profile of iloperidone in the treatment of schizophrenia. Expert Opin Drug Saf. 2014 Feb;13(2):241-6. doi: 10.1517/14740338.2014.854770. Epub 2013 Nov 11. Review. PubMed PMID: 24206391.
2: Rado JT, Janicak PG. Long-term efficacy and safety of iloperidone: an update. Neuropsychiatr Dis Treat. 2014 Feb 26;10:409-15. doi: 10.2147/NDT.S37824. eCollection 2014. Review. PubMed PMID: 24600226; PubMed Central PMCID: PMC3942304.
3: Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU. Asenapine, blonanserin, iloperidone, lurasidone, and sertindole: distinctive clinical characteristics of 5 novel atypical antipsychotics. Clin Neuropharmacol. 2013 Nov-Dec;36(6):223-38. doi: 10.1097/WNF.0b013e3182aa38c4. Review. PubMed PMID: 24201235.
4: Bobo WV. Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults. Expert Rev Clin Pharmacol. 2013 Jan;6(1):61-91. doi: 10.1586/ecp.12.70. Review. PubMed PMID: 23272794.
5: Tarazi FI, Stahl SM. Iloperidone, asenapine and lurasidone: a primer on their current status. Expert Opin Pharmacother. 2012 Sep;13(13):1911-22. doi: 10.1517/14656566.2012.712114. Epub 2012 Jul 31. Review. PubMed PMID: 22849428.
6: De Hert M, Yu W, Detraux J, Sweers K, van Winkel R, Correll CU. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012 Sep 1;26(9):733-59. doi: 10.2165/11634500-000000000-00000. Review. PubMed PMID: 22900950.
7: Weiden PJ. Iloperidone for the treatment of schizophrenia: an updated clinical review. Clin Schizophr Relat Psychoses. 2012 Apr;6(1):34-44. doi: 10.3371/CSRP.6.1.5. Review. PubMed PMID: 22453868.
8: Crabtree BL, Montgomery J. Iloperidone for the management of adults with schizophrenia. Clin Ther. 2011 Mar;33(3):330-45. doi: 10.1016/j.clinthera.2011.03.006. Review. PubMed PMID: 21600386.
9: Citrome L. Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics. Postgrad Med. 2011 Mar;123(2):153-62. doi: 10.3810/pgm.2011.03.2273. Review. PubMed PMID: 21474903.
10: Arif SA, Mitchell MM. Iloperidone: A new drug for the treatment of schizophrenia. Am J Health Syst Pharm. 2011 Feb 15;68(4):301-8. doi: 10.2146/ajhp100079. Review. PubMed PMID: 21289324.
11: Citrome L. Iloperidone: a clinical overview. J Clin Psychiatry. 2011;72 Suppl 1:19-23. doi: 10.4088/JCP.10075su1.04. Review. PubMed PMID: 22217439.
12: Citrome L. Iloperidone: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability, regulatory affairs, and an opinion. Expert Opin Drug Metab Toxicol. 2010 Dec;6(12):1551-64. doi: 10.1517/17425255.2010.531259. Epub 2010 Nov 1. Review. PubMed PMID: 21034370.
13: Bishop JR, Bishop DL. Iloperidone for the treatment of schizophrenia. Drugs Today (Barc). 2010 Aug;46(8):567-79. doi: 10.1358/dot.2010.46.8.1509989. Review. PubMed PMID: 20830317.
14: Rado J, Janicak PG. Iloperidone for schizophrenia. Expert Opin Pharmacother. 2010 Aug;11(12):2087-93. doi: 10.1517/14656566.2010.502889. Review. PubMed PMID: 20586713.
15: Marino J, Caballero J. Iloperidone for the treatment of schizophrenia. Ann Pharmacother. 2010 May;44(5):863-70. doi: 10.1345/aph.1M603. Epub 2010 Apr 13. Review. PubMed PMID: 20388862.
16: Caccia S, Pasina L, Nobili A. New atypical antipsychotics for schizophrenia: iloperidone. Drug Des Devel Ther. 2010 Feb 18;4:33-48. Review. PubMed PMID: 20368905; PubMed Central PMCID: PMC2846148.
17: Cutler AJ. Iloperidone: a new option for the treatment of schizophrenia. Expert Rev Neurother. 2009 Dec;9(12):1727-41. doi: 10.1002/pmic.200800563. Review. PubMed PMID: 19951132.
18: Scott LJ. Iloperidone: in schizophrenia. CNS Drugs. 2009 Oct;23(10):867-80. doi: 10.2165/10489070-000000000-00000. Review. PubMed PMID: 19739696.
19: Citrome L. Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychotic. Int J Clin Pract. 2009 Aug;63(8):1237-48. doi: 10.1111/j.1742-1241.2009.02142.x. Review. PubMed PMID: 19624791.
20: Jain KK. An assessment of iloperidone for the treatment of schizophrenia. Expert Opin Investig Drugs. 2000 Dec;9(12):2935-43. Review. PubMed PMID: 11093363.
