Absorption, Distribution and Excretion
After oral adminitration, perampanel is absorbed rapidly and completely.
Perampanel is eliminated mostely in the feces (48%) and to a lesser exten in the urine (22%).
The volume of distribution of perampanel was not quantified.
In healthy patients, perampanel has a clearance of about 12 mL/min.

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Metabolism / Metabolites
Perampanel is highly metabolized by CYP3A4 and/or CYP3A5 primary oxidation and by sequential glucuronidation.

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Biological Half-Life
Perampanel has a long elmination half-life of about 105 hours.

Hepatotoxicity
Limited data are available on the hepatotoxicity of perampanel. In clinical trials, therapy with perampanel was not associated with an increased frequency of serum aminotransferase elevations as compared to placebo treatment, and there were no reported instances of clinically apparent liver injury. No individual case reports of perampanel hepatotoxicity have been published since its general clinical availability. Perampanel has been implicated in rare instances of severe cutaneous hypersensitivity reactions including DRESS syndrome, which can be associated with variable degrees of liver injury. Thus, clinically apparent liver injury due to perampanel may occur, but must be very rare.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
A minimal amount of information indicates that perampanel milk levels are quite low. If perampanel is required by the mother, it is not a reason to discontinue breastfeeding, but monitor the infant for drowsiness, agitation, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of drugs.
◉ Effects in Breastfed Infants
An infant was exclusively breastfed by a mother taking perampanel, brivaracetam and lacosamide for 6 weeks, then partially breastfed. The infant did not exhibit reduced wakefulness or feeding problems. At one year of age, the mother reported normal development.[1]
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Perampanel is 95-96% plasma protein bound with most binding to the plasma proteins α1-acid glycoprotein and albumin.

Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurol Scand. 2016 Mar;133(3):160-72. doi: 10.1111/ane.12529. Review. PubMed PMID: 26506904; PubMed Central PMCID: PMC4738453.

Perampanel is a member of the class of bipyridines that is 2,3'-bipyridin-6'-one substituted at positions 1' and 5' by phenyl and 2-cyanophenyl groups respectively. Used as an adjunctive therapy for the treatment of partial-onset seizures in patients with epilepsy. It has a role as an AMPA receptor antagonist and an anticonvulsant. It is a pyridone, a nitrile and a member of bipyridines. It is functionally related to a benzonitrile.
Perampanel is a noncompetitive AMPA glutamate receptor antagonist. It is marketed under the name Fycompa™ and is indicated as an adjunct in patients over 12 years old for the treatment of partial-onset seizures that may or may not occur with generalized seizures. The FDA label includes an important black-boxed warning of serious or life-threatening behavioral and psychiatric reactions in patients taking Fycompa™.
Perampanel is a Noncompetitive AMPA Glutamate Receptor Antagonist. The mechanism of action of perampanel is as an AMPA Receptor Antagonist, and UGT2B7 Inhibitor, and UGT1A9 Inhibitor, and Cytochrome P450 3A4 Inhibitor, and Cytochrome P450 2C8 Inhibitor.
Perampanel is glutamate receptor antagonist that is used as an anticonvulsant in the therapy of partial onset seizures. Perampanel has not been associated with serum aminotransferase elevations during therapy, and clinically apparent liver injury from perampanel has yet to be reported and must be rare, if it occurs at all.
Perampanel is an orally active, non-competitive, and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, with anti-epileptic activity. Although the mechanism of action through which perampanel exerts its antiepileptic effect has not been fully elucidated, this agent antagonizes the AMPA subtype of the excitatory glutamate receptor found on postsynaptic neurons in the central nervous system (CNS). This antagonistic action prevents AMPA receptor activation by glutamate and results in the inhibition of neuronal excitation, repetitive neuronal firing, and the stabilization of hyper-excited neural membranes. Glutamate, the primary excitatory neurotransmitter in the CNS, plays an important role in various neurological disorders caused by neuronal hyperexcitation.
See also: Perampanel Hydrate (annotation moved to).

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Drug Indication
Perampanel is indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures in epileptic patients four years of age and older. It is also indicated as an adjunct in the treatment of primary generalized tonic-clonic seizures in epileptic patients aged 12 years and older.
FDA Label
Fycompa is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalised seizures in adult and adolescent patients from 12 years of age with epilepsy. Fycompa is indicated for the adjunctive treatment of primary generalised tonic-clonic seizures in adult and adolescent patients from 12 years of age with idiopathic generalised epilepsy.
Treatment of treatment-resistant epilepsies

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Mechanism of Action
The exact mechanism of action of perampanel in seizures is not yet determined, but it is known that perampanel decreases neuronal excitation by non-competitive ihibition of the AMPA receptor.

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Pharmacodynamics
Perampanel is involved in inhibiting neuronal excitation in the central nervous system leading to such effects as decreased pyschomotor performance.

C23H15N3O

349.38

349.121

380917-97-5

380917-97-5

9924495

Typically exists as solid at room temperature

1.3±0.1 g/cm3

619.1±55.0 °C at 760 mmHg

328.2±31.5 °C

0.0±1.8 mmHg at 25°C

1.706

3.7

0

3

3

27

664

0

O=C1C(C2=C([H])C([H])=C([H])C([H])=C2C#N)=C([H])C(C2=C([H])C([H])=C([H])C([H])=N2)=C([H])N1C1C([H])=C([H])C([H])=C([H])C=1[H]

PRMWGUBFXWROHD-UHFFFAOYSA-N

InChI=1S/C23H15N3O/c24-15-17-8-4-5-11-20(17)21-14-18(22-12-6-7-13-25-22)16-26(23(21)27)19-9-2-1-3-10-19/h1-14,16H

5'-(2-cyanophenyl)-1'-phenyl-2,3'-bipyridinyl-6'(1'H)-one

E 2007 E2007 E-2007 ER15505590 ER 15505590 Perampanel Fycompa Related CAS#

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)