Pitolisant: Difference between revisions
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| bioavailability = Not formally established; oral once-daily adequate | | bioavailability = Not formally established; oral once-daily adequate | ||
| pregnancy = Limited data; pitolisant may reduce hormonal contraceptive efficacy | | pregnancy = Limited data; pitolisant may reduce hormonal contraceptive efficacy | ||
| legal = Rx | | legal = Rx, '''not a controlled substance''' (unique among wake-promoting agents) | ||
| intro = '''Pitolisant''' (brand name Wakix) is a selective histamine H3 receptor inverse agonist FDA-approved in August 2019 for excessive daytime sleepiness and cataplexy in narcolepsy. Notable for being '''not a controlled substance''' | | intro = '''Pitolisant''' (brand name Wakix) is a selective histamine H3 receptor inverse agonist FDA-approved in August 2019 for excessive daytime sleepiness and cataplexy in narcolepsy. Notable for being '''not a controlled substance''', unique among approved wake-promoting medicines, all of which have abuse potential and DEA scheduling (modafinil IV, methylphenidate II, amphetamine II, solriamfetol IV, sodium oxybate III). | ||
Mechanism: H3 autoreceptors on histamine neurons in the tuberomammillary nucleus normally inhibit histamine release. Pitolisant blocks (or inverse-agonizes) these autoreceptors, disinhibiting histamine release and promoting wakefulness. Downstream effects on acetylcholine, norepinephrine, and dopamine pathways may also contribute. Slow titration required. | Mechanism: H3 autoreceptors on histamine neurons in the tuberomammillary nucleus normally inhibit histamine release. Pitolisant blocks (or inverse-agonizes) these autoreceptors, disinhibiting histamine release and promoting wakefulness. Downstream effects on acetylcholine, norepinephrine, and dopamine pathways may also contribute. Slow titration required. | ||
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[[Category: | [[Category:Psychostimulants]] | ||
[[Category:Eugeroics | [[Category:Eugeroics]] | ||
[[Category:Psychostimulants]] | [[Category:Psychostimulants]] | ||
[[Category:Histamine H3 Antagonists / Inverse Agonists]] | [[Category:Histamine H3 Antagonists / Inverse Agonists]] | ||
[[Category:Histamine Modulators]] | [[Category:Histamine Modulators]] | ||
Latest revision as of 17:01, 21 May 2026
Histamine H3 receptor inverse agonist / antagonist, wake-promoting agent
Pitolisant
Wakix
Pitolisant (brand name Wakix) is a selective histamine H3 receptor inverse agonist FDA-approved in August 2019 for excessive daytime sleepiness and cataplexy in narcolepsy. Notable for being not a controlled substance, unique among approved wake-promoting medicines, all of which have abuse potential and DEA scheduling (modafinil IV, methylphenidate II, amphetamine II, solriamfetol IV, sodium oxybate III).
Mechanism: H3 autoreceptors on histamine neurons in the tuberomammillary nucleus normally inhibit histamine release. Pitolisant blocks (or inverse-agonizes) these autoreceptors, disinhibiting histamine release and promoting wakefulness. Downstream effects on acetylcholine, norepinephrine, and dopamine pathways may also contribute. Slow titration required.
High-affinity inverse agonist at human H3 receptor. Minimal binding at H1, H2, H4, monoamine transporters, or other monoamine receptors.
Experience
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Problems
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+ Add a problemTitration strategies
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Effects
Headache, insomnia, anxiety, nausea, abdominal pain, decreased appetite, sleep disturbances. QT prolongation possible (caution with other QT-prolonging medicines). Can reduce hormonal contraceptive efficacy.
Pharmacodynamics
Interactions
No interactions reported yet.
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Relevant Literature
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Pharmacy
Starting dose
Week 1: 8.9 mg PO once daily in the morning. Week 2: 17.8 mg. Week 3+: 35.6 mg (max). Titrate as needed.
Preparations
4.45 mg, 17.8 mg tablets
US FDA Max
35.6 mg/d
Common uses
Classification(s)
Classes
Histamine H3 receptor inverse agonist / antagonist, wake-promoting agent
Pharmacology
Routes
Oral
Onset
Wake-promoting effect over weeks of titration
Duration
Daily morning dosing
Half-life
~20 hours
Bioavailability
Not formally established; oral once-daily adequate
Pregnancy
Limited data; pitolisant may reduce hormonal contraceptive efficacy
Legal status
Rx, not a controlled substance (unique among wake-promoting agents)
Purported mechanism
Selective inverse agonist (or antagonist depending on assay) at presynaptic histamine H3 autoreceptors. H3 receptors normally inhibit histamine release; blocking them disinhibits histamine release from tuberomammillary nucleus, promoting wakefulness. Also enhances acetylcholine, norepinephrine, dopamine release (downstream of histamine signaling).
Pharmacopedia is intended for reference. Nothing here is advice. In an emergency call 911; US Poison Control 1-800-222-1222. See the full disclaimer.