title: Efficacy of the histamine 3 receptor (H3R) antagonist pitolisant (formerly known as tiprolisant; BF2.649) in epilepsy: dose-dependent effects in the human photosensitivity model.
abstract: A new class of drugs, the nonimidazole histamine 3 receptor (H3R) antagonists, has been developed in the past decade for treatment of various brain diseases. Pitolisant is such a drug. We studied the pharmacodynamic effect of pitolisant in patients with epilepsy in early Phase II, using the photosensitivity proof of concept model. A total of 14 adult patients (11 females and 3 males; 5 drug naïve) were studied for three days to evaluate the effect of a single oral dose of pitolisant on EEG photosensitivity ranges. All patients showed repeatedly a generalized photoparoxysmal response (PPR) prior to drug administration on placebo Day 1. A statistically significant suppressive effect (standardized photosensitive response [SPR] reduction as measured with paired t-tests) for 20-, 40-, or 60-mg doses of pitolisant was seen in 9/14 (64%) patients of whom 6/14 (43%) showed abolition of the response to intermittent photic stimulation (IPS). Patients on the highest dosage (60 mg) showed the strongest effect with an effect lasting up to 28 h. Thus, full-scale Phase II studies with this novel H3R antagonist, pitolisant, in patients with epilepsy are warranted.
authors.affiliation: University of Rome Sapienza II, Rome, Italy. dkasteleijn@planet.nl
authors.forename: Dorothée
authors.initials: D
authors.lastname: Kasteleijn-Nolst Trenité
authors.forename: Dominique
authors.initials: D
authors.lastname: Parain
authors.forename: Pierre
authors.initials: P
authors.lastname: Genton
authors.forename: Pascal
authors.initials: P
authors.lastname: Masnou
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Edouard
authors.initials: E
authors.lastname: Hirsch
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004597:Electroshock / Q000009:adverse effects / Q000145:classification; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000209:etiology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D010880:Piperidines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D010880:Piperidines; C516975:pitolisant; D007608:Kainic Acid