Iloperidone

Names

[ Name ]:
Iloperidone

[Synonym ]:
1-(4-{3-[4-(6-Fluoro-1,2-benzoxazol-3-yl)-1-piperidinyl]propoxy}-3-methoxyphenyl)ethanone
1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanone
Zomaril
iloperidone
1-(4-(3-(4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl)propoxy)-3-methoxyphenyl)ethanone
Fanapta
Ethanone, 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-
1-(4-{3-[4-(6-Fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy}-3-methoxyphenyl)ethanone
Fanapt

Biological Activity

[Description]:

Iloperidone(HP 873) is a D2/5-HT2 receptor antagonist, which is an atypical antipsychotic for the treatment of schizophrenia symptoms.IC50 value:Target: 5-HT receptor; D2 receptorIloperidone (HP 873) is a compound currently in clinical trials for the treatment of schizophrenia. Iloperidone displays affinity for dopamine D2 receptors and for 5-HT2A receptors and has a variety of in vivo activities suggestive of an atypical antipsychotic. Iloperidone displayed higher affinity for the dopamine D3 receptor (Ki = 7.1 nM) than for the dopamine D4 receptor (Ki = 25 nM). Iloperidone displayed high affinity for the 5-HT6 and 5-HT7 receptors (Ki = 42.7 and 21.6 nM, respectively), and was found to have higher affinity for the 5-HT2A (Ki = 5.6 nM) than for the 5-HT2C receptor (Ki = 42.8 nM) [1]. Iloperidone was eliminated slowly, with a mean t1/2 of 13.5 to 14.0 hours. Coadministration with food did not significantly affect AUC, tmax, or Cmax. These results indicate that the rate of iloperidone's absorption is decreased, but the overall bioavailability is unchanged, when the drug is taken with food. Orthostatic hypotension, dizziness, and somnolence were the most commonly reported adverse events [2]. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results [3].Clinical indications: Post traumatic stress disorder; Schizophrenia Toxicity: Commonly observed adverse reactions (incidence ≥5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

Signaling Pathways >> GPCR/G Protein >> Dopamine Receptor

Signaling Pathways >> Neuronal Signaling >> Dopamine Receptor

Research Areas >> Neurological Disease

[References]

[1]. Kongsamut, S., et al., Iloperidone binding to human and rat dopamine and 5-HT receptors. Eur J Pharmacol, 1996. 317(2-3): p. 417-23.

[2]. Sainati, S.M., et al., Safety, tolerability, and effect of food on the pharmacokinetics of iloperidone (HP 873), a potential atypical antipsychotic. J Clin Pharmacol, 1995. 35(7): p. 713-20.

[3]. Albers, L.J., A. Musenga, and M.A. Raggi, Iloperidone: a new benzisoxazole atypical antipsychotic drug. Is it novel enough to impact the crowded atypical antipsychotic market? Expert Opin Investig Drugs, 2008. 17(1): p. 61-75.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
593.7±50.0 °C at 760 mmHg

[ Melting Point ]:
118-120°C

[ Molecular Formula ]:
C₂₄H₂₇FN₂O₄

[ Molecular Weight ]:
426.481

[ Flash Point ]:
312.8±30.1 °C

[ Exact Mass ]:
426.195496

[ PSA ]:
64.80000

[ LogP ]:
3.81

[ Appearance of Characters ]:
white to beige

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.570

[ Storage condition ]:
-20°C Freezer, Under Inert Atmosphere

[ Water Solubility ]:
DMSO: soluble5mg/mL, clear

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS02, GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H225-H301 + H311 + H331-H370

[ Precautionary Statements ]:
P210-P260-P280-P301 + P310-P311

[ Hazard Codes ]:
F,T

[ Risk Phrases ]:
11-23/24/25-39/23/24/25

[ Safety Phrases ]:
16-36/37-45

[ RIDADR ]:
UN2811 - class 6.1 - PG 3 - EHS - Toxic solids, organic, n.o.s., HI: all

[ RTECS ]:
KM5777850

[ HS Code ]:
2934999090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

A thorough QTc study of 3 doses of iloperidone including metabolic inhibition via CYP2D6 and/or CYP3A4 and a comparison to quetiapine and ziprasidone.

J. Clin. Psychopharmacol. 33(1) , 3-10, (2013)

The potential for iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate-corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-la...

Long-term safety and tolerability of iloperidone: results from a 25-week, open-label extension trial.

CNS Spectr. 18(1) , 43-54, (2013)

Long-term use of the atypical antipsychotic iloperidone has not been investigated at doses above 16 mg/d. This article describes safety and tolerability results from the 25-week open-label extension o...

Stable-isotope dilution LC-MS/MS assay for determination of iloperidone and its two major metabolites, P 88 and P 95, in human plasma: application to a bioequivalence study.

Bioanalysis 5(6) , 669-86, (2013)

Iloperidone is a novel antipsychotic drug with high affinity for serotonin and D(2) dopamine receptors. A sensitive and rapid isotope dilution LC-MS/MS method has been developed for the simultaneous d...