Pitolisant: Difference between revisions

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{{MedTemplate

| ~~generic~~ = ~~Pitolisant~~

| brand = Wakix

| ~~brand~~ = ~~Wakix~~

| classes = Histamine H3 receptor inverse agonist / antagonist, wake-promoting agent

| ~~classes~~ = ~~Eugeroic~~

| 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).

| ~~mechanism~~ = ~~Histamine~~ H3 receptor inverse agonist/~~antagonist~~

| 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:Histamine H3 Antagonists / Inverse Agonists]]

[[Category:Histamine Modulators]]

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