380917-97-5 Usage
Uses
Used in Pharmaceutical Industry:
Perampanel is used as an antiepileptic drug for the treatment of partial onset seizures in epileptic patients who are at least 12 years old. It selectively blocks AMPA receptor-mediated synaptic transmission, reducing neuronal excitation and helping to control seizures.
Used in Neurological Applications:
Perampanel is used as a treatment for epilepsy, specifically targeting AMPA-induced increases in intracellular Ca2+. By inhibiting this process, perampanel helps to prevent the excessive neuronal activity that leads to seizures, providing a valuable therapeutic option for patients with epilepsy.
Indications
Epilepsy: Adjunctive treatment of focal seizures with or without secondary generalization and primary generalized tonic- clonic seizures.
Dose titration
Epilepsy— adjunctive therapy: 2 mg nocte for at least 14 days, then increased by 2 mg every 14 or more days; usual maintenance 4– 8 mg nocte (max. 12 mg nocte).
Interactions
With AEDs
Some AEDs known as CYP450 3A enzyme inducers (carbamazepine, oxcarbazepine, phenytoin) have been shown to increase perampanel clearance and consequently to decrease plasma concentrations of perampanel. Carbamazepine, a known potent enzyme inducer, reduced perampanel levels by two- thirds in a study performed on healthy subjects
In the epilepsy population pharmacokinetic analysis, perampanel was found to decrease the clearance of oxcarbazepine by 26%. Oxcarbazepine is rapidly metabolized by cytosolic reductase enzyme to the active metabolite, monohydroxycarbazepine. The effect of perampanel on monohydroxycarbazepine concentrations is not known.
With other drugs
Strong inducers of cytochrome P450, such as rifampicin and St John’s Wort (Hypericum perforatum), are expected to decrease perampanel concentrations.
In healthy subjects, the CYP3A4 inhibitor ketoconazole increases perampanel exposure.
Perampanel can make certain hormonal contraceptives such as levonorgestrel less effective.
Decrease in exposure of midazolam may be caused by perampanel.
With alcohol/food
Drinking alcohol while taking perampanel can affect a patients’ alertness and ability to drive or use tools or machines. It can also aggravate irritability, confusion, and depression.
There are no specific foods that must be excluded from diet when taking perampanel.
Special populations
Hepatic impairment
Increase at intervals of at least 2 weeks, up to a maximum of 8 mg daily, in mild- to- moderate impairment.
Avoid in severe impairment.
Renal impairment
Avoid in moderate or severe impairment.
Pregnancy
There are limited amount of data available on the use of perampanel in pregnant women and the potential risk for humans is unknown.
Perampanel is not recommended in pregnancy and female patients must use a reliable method of contraception to avoid becoming pregnant while being treated with perampanel (this should be continued for 1?month after stopping treatment).
As perampanel can make certain hormonal contraceptives such as levonorgestrel less effective, other forms of safe and effective contraception (such as a condom or coil) should be used when taking perampanel (this should be continued for 1 month after stopping treatment).
Perampanel has been found to be present in milk in animal studies and it is recommended that breastfeeding should be avoided.
Behavioural and cognitive effects in patients with epilepsy
For this third- generation agent, clinical experience is still limited, and little is known about its positive and negative psychotropic properties, and their implications for the management of behavioural symptoms in patients with epilepsy. There are initial reports of behavioural disturbances (especially depression, anxiety, irritability, and psychosis), which seem to be dose- related and tend to appear within the first weeks of treatment. Reports of cognitive effects (mainly affecting memory) are relatively rare.
Psychiatric use
Perampanel has no indications for the treatment of psychiatric disorders. There is insufficient experience with perampanel to draw any conclusion regarding its psychotropic profile.
Originator
Eisai (Japan)
Clinical Use
Selective AMPA-type glutamate receptor antagonist:
Antiepileptic
Drug interactions
Potentially hazardous interactions with other drugs
Antidepressants: anticonvulsant effect antagonised;
avoid with St John’s wort.
Antiepileptics: concentration reduced by
carbamazepine, fosphenytoin, oxcarbazepine and
phenytoin.
Antimalarials: anticonvulsant effect antagonised by
mefloquine.
Antipsychotics: anticonvulsant effect antagonised.
Orlistat: possibly increased risk of convulsions.
Progestogens: high-dose perampanel reduces plasma
concentration of progestogens (possibly reduced
contraceptive effect).
Metabolism
Extensively metabolised via primary oxidation via the
cytochrome P450 isoenzyme CYP3A sub family and
sequential glucuronidation.
Perampanel is excreted in the urine and faeces mainly as
oxidative and conjugated metabolites.
Check Digit Verification of cas no
The CAS Registry Mumber 380917-97-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,8,0,9,1 and 7 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 380917-97:
(8*3)+(7*8)+(6*0)+(5*9)+(4*1)+(3*7)+(2*9)+(1*7)=175
175 % 10 = 5
So 380917-97-5 is a valid CAS Registry Number.
380917-97-5Relevant articles and documents
Simple preparation method of perampanel
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, (2019/08/01)
The invention relates to a simple preparation method of perampanel. The method comprises: (1) carrying out an amidation reaction on a compound represented by a formula II and a compound represented bya formula III in a solvent or under a solvent-free condition to prepare a compound represented by a formula IV; and (2) carrying out condensation on the compound represented by the formula IV and a methylenenation reagent in a solvent in the presence of a catalyst to obtain a compound represented by a formula V, and removing hydrogen cyanide or hydrogen chloride under the action of an alkaline reagent to form a ring so as to prepare perampanel. According to the present invention, the method has advantages of cheap and easily available raw materials, simple process operation, high reaction selectivity of the unit, high yield and high purity of the product, less three-waste, high reaction atom economy and environmental protection.
NOVEL PROCESS FOR THE PREPARATION OF PERAMPANEL AND ITS INTERMEDIATES THEREOF
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, (2016/10/04)
The present invention provides novel process for preparation of 3-(2-cyanophenyl)-5-(2- pyridyl)-1-phenyl-1,2-dihydropyridin-2-one, commonly known as perampanel having the formula I. The present invention also provides novel intermediate compound of formula VI and process for the preparation of intermediate compound of formula VI. The present invention also provides purification of perampanel.
PROCESS AND INTERMEDIATES FOR THE PREPARATION OF PERAMPANEL
-
, (2016/09/15)
The present invention describes a process for the synthesis of 3-(2-cyanophenyl)-5-(2- pyridyl)-1-phenyl-1,2-dihydro-pyridin-2-one (Perampanel) represented by the structure of formula (1), and salts thereof, especially salts with pharmaceutically acceptable acids. The present invention further relates to certain intermediates formed and/or used in such process.
PROCESS FOR THE PREPARATION OF PERAMPANEL
-
, (2016/04/26)
The present invention relates to processes for the preparation of perampanel and its intermediates.
PROCESS FOR THE PREPARATION OF PERAMPANEL
-
, (2015/02/19)
The present invention provides intermediates useful for the synthesis of Perampanel and processes employing said intermediates for preparing Perampanel. The invention also provides processes for making the intermediates, crystalline forms of the intermediates and the use of the crystalline forms for preparing Perampanel.
Discovery of 2-(2-Oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl) benzonitrile (Perampanel): A novel, noncompetitive α-amino-3-hydroxy-5- methyl-4-isoxazolepropanoic acid (AMPA) receptor antagonist
Hibi, Shigeki,Ueno, Koshi,Nagato, Satoshi,Kawano, Koki,Ito, Koichi,Norimine, Yoshihiko,Takenaka, Osamu,Hanada, Takahisa,Yonaga, Masahiro
, p. 10584 - 10600 (2013/02/23)
Dysfunction of glutamatergic neurotransmission has been implicated in the pathogenesis of epilepsy and numerous other neurological diseases. Here we describe the discovery of a series of 1,3,5-triaryl-1H-pyridin-2-one derivatives as noncompetitive antagonists of AMPA-type ionotropic glutamate receptors. The structure-activity relationships for this series of compounds were investigated by manipulating individual aromatic rings located at positions 1, 3, and 5 of the pyridone ring. This culminated in the discovery of 2-(2-oxo-1-phenyl-5- pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile (perampanel, 6), a novel, noncompetitive AMPA receptor antagonist that showed potent activity in an in vitro AMPA-induced Ca2+ influx assay (IC50 = 60 nM) and in an in vivo AMPA-induced seizure model (minimum effective dose of 2 mg/kg po). Perampanel is currently in regulatory submission for partial-onset seizures associated with epilepsy.
A practical, laboratory-scale synthesis of Perampanel
McElhinny Jr., Charles J.,Carroll,Lewin, Anita H.
, p. 57 - 62 (2012/04/10)
The orally active, noncompetitive, selective AMPA receptor antagonist Perampanel, 2-[1,6-dihydro-6-oxo-1-phenyl-(2,3-bipyridin)-5-yl]benzonitrile, has been prepared from readily available, relatively inexpensive starting materials. The synthesis was carried out on a laboratory scale with no specialized equipment, and involved only two chromatographic purifications. Georg Thieme Verlag Stuttgart. New York.
CRYSTAL OF 1,2-DIHYDROPYRIDINE COMPOUND (TYPE IV)
-
Page/Page column 4, (2009/04/24)
A crystal of 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one characterized in having a diffraction peak at a diffraction angle (2θ±0.2°) of 15.4° in a powder X-ray diffraction or others.
AMORPHOUS FORM OF 1,2-DIHYDROPYRIDINE COMPOUND
-
Page/Page column 6, (2008/12/08)
An amorphous form of 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridine-2-one.
CRYSTAL OF 1,2-DIHYDROPYRIDINE COMPOUND AND METHOD FOR PRODUCING SAME
-
Page/Page column 12, (2008/06/13)
The invention provides crystals of 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one and production processes therefor.
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