Perampanel

Key takeaways

Perampanel belongs to chemistry; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Perampanel to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Perampanel from memory before moving on to harder problems.

Reference excerpt

Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai that is used in addition to other medications to treat partial seizures and generalized tonic–clonic seizures. Perampanel is a non-competitive AMPA glutamate receptor antagonist. It is taken by mouth. Perampanel was approved in 2012, and as of 2016, its optimal role in the treatment of epilepsy relative to other drugs is not clear. It is the first anti-epileptic drug in the class of selective non-competitive antagonist of AMPA receptors. The US prescribing information has a boxed warning that perampanel may cause serious psychiatric and behavioral changes; it may cause homicidal or suicidal thoughts. Other side effects have included dizziness, somnolence, vertigo, aggression, anger, loss of coordination, blurred vision, irritability, and slurred speech. Perampanel reduced the effectiveness of levonorgestrel oral contraceptives by about 40%. Women who may get pregnant should not take it as studies in animals show it may harm a fetus. Perampanel is liable to be abused; very high doses produced euphoria responses similar to ketamine. It is designated as a Schedule III controlled substance by the US Drug Enforcement Administration. Perampanel is authorized as a generic medication.

Medical uses Perampanel is used in addition to other drugs to treat partial seizures and generalized tonic–clonic seizures for people older than twelve years. In the US, perampanel is indicated for the treatment of partial-onset seizures with or without secondarily generalized seizures in people with epilepsy aged four years of age and older; and for adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in people with epilepsy aged twelve years of age and older. In the EU, perampanel is indicated for the adjunctive treatment of partial-onset seizures with or without secondarily generalized seizures in people aged twelve years of age and older with epilepsy; and for the adjunctive treatment of primary generalized tonic-clonic seizures in people aged twelve years of age and older with idiopathic generalized epilepsy.

Contraindications Based on animal data, perampanel may cause fetal harm; it is not recommended for women of child-bearing age not taking contraception. People with severe liver impairment or severe kidney disease, including those on dialysis, should not take perampanel.

Side effects Perampanel's label has a black box warning noting that some people taking the drug have undergone serious psychiatric and behavioral changes. These events occurred in people who had no history of such issues, as well as people who had such a history. The psychiatric changes included mood changes such as euphoria, anger, irritability, aggression, belligerence, agitation, and anxiety, as well as psychosis and delirium. Behavioral changes included physical assault and homicidal ideation or threats. Other serious side effects include suicidal thoughts or behavior, dizziness and gait disturbance, somnolence and fatigue, risk of falls, and increased risk of seizures if the drug is quickly withdrawn. In clinical trials, dizziness, somnolence, vertigo, aggression, anger, loss of coordination, blurred vision, irritability, and slurred speech were the side effects that most commonly led people to leave the trial. Perampanel is liable to be abused: very high doses produced euphoria responses and dissociative effects similar to ketamine, although subjects liked it less and had experienced it more negatively than ketamine. It is designated as a Schedule III controlled substance by the Drug Enforcement Administration. A study of dependence in rats found withdrawal symptoms when the drug was removed; dependence in humans wasn't studied well enough to make generalizations as of April 2016. There is limited experience with overdose.

Interactions Perampanel reduced the effectiveness of levonorgestrel oral contraceptives by about 40%. Other antieptilectic drugs that induce cytochrome P450, including carbamazepine, phenytoin, and oxcarbazepine decrease the effectiveness of perampanel by 50-67%. Use of perampanel with strong CYP3A inducers like rifampin or St. John's wort is not recommended. Use of perampanel with CNS depressants like alcohol may increase the effect of the CNS depressant.

Pharmacology Perampanel is a selective non-competitive antagonist of AMPA receptors, the major subtype of ionotropic glutamate receptors. It was the first drug of this class approved for epilepsy. Whole-cell voltage clamp studies have demonstrated that perampanel is a negative allosteric AMPA receptor antagonist. Perampanel caused a slow (τ~1 s at 3 μM), concentration-dependent inhibition of AMPA receptor currents. The rates of block and unblock of AMPA receptor currents were 1.5×105 M−1 s−1 and 0.58 s−1, respectively. Perampanel did not affect NMDA receptor currents. The extent of block (IC50, 0.56 μM) was similar at all agonist concentrations, demonstrating a noncompetitive blocking action. Parampanel did affect AMPA receptor desensitization, or the ratio of peak to late response to rapid application of AMPA. Perampanel is a selective negative allosteric AMPA receptor antagonist of high-affinity and slow blocking kinetics, and is not use-dependent. Perampanel has a prolonged terminal half-life in humans of approximately 105 hours. The drug is 95% bound to plasma protein. Its primary route of metabolism is by CYP3A4. It does not induce P450 enzymes. About 70% of the dose is excreted in the feces and 30% in the urine; less than 2% of the dose is excreted unchanged into the urine.

Chemistry The chemical formula of perampanel is 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile; it has a bipyridine core structure that sets it apart from other AMPA receptor antagonists. The tablets contain lactose monohydrate, low substituted hydroxypropyl cellulose, povidone, microcrystalline cellulose, magnesium stearate, hypromellose, polyethylene glycol, talc, and titanium dioxide in addition to the API; the oral suspension contains sorbitol, microcrystalline cellulose, carboxymethylcellulose sodium, poloxamer, simethicone, citric acid, sodium benzoate and purified water in addition to the API.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Perampanel

Start with the simplest possible case. Write down what Perampanel claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Perampanel before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Perampanel ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Perampanel

In research: Perampanel appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Perampanel in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Perampanel is common in secondary-school and first-year university syllabi. It links to neighbouring topics 2-Pyridones, 2-Pyridyl compounds, AMPA receptor antagonists, so understanding it makes those chapters shorter.
In everyday life: Look for Perampanel outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Perampanel in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Perampanel means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Perampanel out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Perampanel in simple terms?

Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai that is used in addition to other medications to treat partial seizures and generalized tonic–clonic seizures. Perampanel is a non-competitive AMPA glutamate receptor antagonist.

Why does Perampanel matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Perampanel?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Perampanel.