Pitolisant

Key takeaways

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

Reference excerpt

Pitolisant, sold under the brand name Wakix among others, is a medication used for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is an inverse agonist of the histamine H3 receptor. It is the first commercially available medication in its class; the U.S. Food and Drug Administration (FDA) designated it a first-in-class medication. Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness. It was approved by the European Medicines Agency (EMA) in March 2016 for narcolepsy with or without cataplexy, and for excessive daytime sleepiness by the FDA in August 2019. The most common side effects include difficulty sleeping, nausea, and feeling worried.

Medical uses Pitolisant is indicated in adults for the treatment of narcolepsy. Narcolepsy is a chronic sleep disorder that causes overwhelming daytime drowsiness. Pitolisant is also indicated to improve alertness and reduce excessive daytime sleepiness in adults with obstructive sleep apnea.

Side effects The most common side effects include insomnia, headache, nausea, anxiety, irritability, dizziness, depression, tremor, sleep disorders, tiredness, vomiting, vertigo, dyspepsia, and heartburn. Rare but serious side effects are abnormal weight loss and spontaneous abortion.

Pharmacology Pitolisant is an inverse agonist of the histamine H3 autoreceptor. The H3 autoreceptors regulate histaminergic activity in the central nervous system (and to a lesser extent, the peripheral nervous system) by inhibiting histamine synthesis and release upon binding to endogenous histamine. By preventing the binding of endogenous histamine at the H3, as well as producing a response opposite to that of endogenous histamine at the receptor (inverse agonism), pitolisant enhances histaminergic activity in the brain. Pitolisant is a drug that belongs to the class of central nervous system (CNS) stimulants. Pitolisant is also considered a eugeroic, which means that it promotes wakefulness and alertness. Eugeroics are different from traditional CNS stimulants such as amphetamine in that they have fewer side effects and lower abuse potential. Pitolisant is the first eugeroic drug that acts by blocking the histamine H3 autoreceptor, which increases the activity of histamine neurons in the brain. Pitolisant has been shown to be effective and well-tolerated for the treatment of narcolepsy with or without cataplexy.

Pitolisant has been demonstrated to exhibit high affinity for sigma-1 and sigma-2 receptors, as well as moderate affinity for 5-HT2A and D3 receptors. There exist conflicting findings relating the intrinsic activity of pitolisant at the 5-HT2A receptor. Pharmacokinetics Pitolisant is readily absorbed when taken by mouth and reaches peak blood concentrations approximately 3 hours after administration. The biological half-life of Pitolisant ranges from 10 to 12 hours.

History Pitolisant is marketed in the European Union by Bioprojet Pharma. It was approved for medical use in the European Union in March 2016 by the European Medicines Agency (EMA). The U.S. Food and Drug Administration (FDA) approved pitolisant for excessive daytime sleepiness in participants with narcolepsy based primarily on evidence from two trials (Trial 1/NCT01067222, Trial 2/NCT01638403). An additional trial (Trial 3/NCT01800045), in which participants with a different type of narcolepsy were exposed to the same dose of pitolisant, was used to add data for evaluation of side effects. The trials were conducted in Europe and South America. The two primary trials enrolled adults with narcolepsy and excessive daytime sleepiness. Participants received pitolisant, placebo, or an approved drug for narcolepsy for eight weeks. For participants receiving pitolisant, the dose could be increased during the first three weeks but had to remain the same for the next five weeks. Neither the participants nor the healthcare providers knew which treatment was being given during the trial. The benefit of pitolisant was evaluated by comparing changes in daytime sleepiness during the trial between pitolisant- and placebo-treated participants. To measure the daytime sleepiness, the investigators used a scale called the Epworth Sleepiness Scale (ESS). The ESS asks participants to rate the likelihood that they would fall asleep while doing eight daily activities (such as sitting and reading or watching television). Participants rate each item from zero (would never doze) to three (high chance of dozing). Pitolisant was approved by the FDA in August 2019. It was granted orphan drug designation for the treatment of narcolepsy, fast track designation for the treatment of excessive daytime sleepiness and cataplexy in people with narcolepsy, and breakthrough therapy designation for the treatment of cataplexy in people with narcolepsy.

Society and culture

Legal status Pitolisant is approved in the European Union and the United States to treat narcolepsy, and is not a controlled substance in these countries. Still, long-term studies comparing the effectiveness and tolerability of pitolisant with modafinil or sodium oxybate are lacking. Pitolisant, the only non-controlled anti-narcoleptic drug in the US, has shown minimal abuse risk in studies.

See also List of investigational narcolepsy and hypersomnia drugs List of investigational Prader–Willi syndrome drugs

References

External links Clinical trial number NCT01067222 for "Efficacy and Safety Study of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy (Harmony1)" at ClinicalTrials.gov Clinical trial number NCT01638403 for "Effects of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy." at ClinicalTrials.gov

Illustrations

Worked examples

Example 1 — a first encounter with Pitolisant

Start with the simplest possible case. Write down what Pitolisant 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 Pitolisant 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 Pitolisant 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 Pitolisant

In research: Pitolisant 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 Pitolisant 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: Pitolisant is common in secondary-school and first-year university syllabi. It links to neighbouring topics 1,3-Propanediyl compounds, 1-Piperidinyl compounds, 4-Chlorophenyl compounds, so understanding it makes those chapters shorter.
In everyday life: Look for Pitolisant 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 Pitolisant in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Pitolisant 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 Pitolisant out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Pitolisant in simple terms?

Pitolisant, sold under the brand name Wakix among others, is a medication used for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is an inverse agonist of the histamine H3 receptor.

Why does Pitolisant 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 Pitolisant?

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 Pitolisant.