Back to Search
Start Over
Preclinical evaluation of the abuse potential of Pitolisant, a histamine H₃ receptor inverse agonist/antagonist compared with Modafinil
- Source :
- British journal of pharmacology. 169(3)
- Publication Year :
- 2012
-
Abstract
- Pitolisant, a histamine H₃ receptor inverse agonist/antagonist is currently under Phase III clinical trials for treatment of excessive daytime sleepiness namely in narcoleptic patients. Its drug abuse potential was investigated using in vivo models in rodents and monkeys and compared with those of Modafinil, a psychostimulant currently used in the same indications.Effects of Pitolisant on dopamine release in the nucleus accumbens, on spontaneous and cocaine-induced locomotion, locomotor sensitization were monitored. It was also tested in three standard drug abuse tests i.e. conditioned place preference in rats, self-administration in monkeys and cocaine discrimination in mice as well as in a physical dependence model.Pitolisant did not elicit any significant changes in dopaminergic indices in rat nucleus accumbens whereas Modafinil increased dopamine release. In rodents, Pitolisant was without any effect on locomotion and reduced the cocaine-induced hyperlocomotion. In addition, no locomotor sensitization and no conditioned hyperlocomotion were evidenced with this compound in rats whereas significant effects were elicited by Modafinil. Finally, Pitolisant was devoid of any significant effects in the three standard drug abuse tests (including self-administration in monkeys) and in the physical dependence model.No potential drug abuse liability for Pitolisant was evidenced in various in vivo rodent and primate models, whereas the same does not seem so clear in the case of Modafinil.
- Subjects :
- Male
Behavior, Animal
Dose-Response Relationship, Drug
Drug Inverse Agonism
Dopamine
Dopaminergic Neurons
Drug Evaluation, Preclinical
Histamine Antagonists
Modafinil
Drugs, Investigational
Wakefulness-Promoting Agents
Motor Activity
Macaca mulatta
Research Papers
Nucleus Accumbens
Rats
Behavior, Addictive
Histamine Agonists
Mice
Piperidines
Animals
Receptors, Histamine H3
Central Nervous System Stimulants
Benzhydryl Compounds
Drug Antagonism
Subjects
Details
- ISSN :
- 14765381
- Volume :
- 169
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- British journal of pharmacology
- Accession number :
- edsair.pmid..........7b87bf723143251bcf1562ff8530d5fb