Pitolisant: Difference between revisions
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{{MedTemplate | {{MedTemplate | ||
| | | brand = Wakix | ||
| | | classes = Histamine H3 receptor inverse agonist / antagonist, wake-promoting agent | ||
| | | 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). | ||
| | | uses = Excessive daytime sleepiness or cataplexy in adults with narcolepsy (FDA-approved August 2019) | ||
| 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 | |||
| fda_max = 35.6 mg/d | |||
| routes = Oral | |||
| onset = Wake-promoting effect over weeks of titration | |||
| duration = Daily morning dosing | |||
| halflife = ~20 hours | |||
| bioavailability = Not formally established; oral once-daily adequate | |||
| pregnancy = Limited data; pitolisant may reduce hormonal contraceptive efficacy | |||
| 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''', 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. | |||
| pharmacodynamics= High-affinity inverse agonist at human H3 receptor. Minimal binding at H1, H2, H4, monoamine transporters, or other monoamine receptors. | |||
| 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. | |||
| interactions = <pharmaInteractions/> | |||
}} | }} | ||
[[Category:Psychostimulants]] | |||
[[Category:Eugeroics]] | |||
[[Category:Psychostimulants]] | [[Category:Psychostimulants]] | ||
[[Category:Histamine H3 Antagonists / Inverse Agonists]] | |||
[[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
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Summary
Classes
Histamine H3 receptor inverse agonist / antagonist, wake-promoting agent
Common uses
Excessive daytime sleepiness or cataplexy in adults with narcolepsy (FDA-approved August 2019)
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
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).