Central and peripheral evaluation of rupatadine, a new antihistamine/platelet-activating factor antagonist, at different doses in healthy volunteers

Neuropsychobiology. 2004;50(4):311-21. doi: 10.1159/000080959.


Aims: To assess peripheral anti-H1 and central nervous system (CNS) activity of single increasing doses of rupatidine fumarate (RU), a new antihistamine/platelet-activating factor antagonist compound, in comparison with hydroxyzine and placebo.

Methods: Eighteen healthy young subjects of both sexes took part in a crossover, randomised, double-blind, placebo-controlled study. Treatments tested were: RU 10, 20, 40 and 80 mg and hydroxyzine 25 mg, as a positive standard. Before and several times after drug intake, peripheral anti-H1 activity was appraised by the skin reactivity to intradermal injection of histamine. CNS effects were also obtained by objective tests of psychomotor performance and subjective mood scales.

Results: All active treatments showed a significant reduction of the wheal and flare reaction in relation to placebo, RU displaying a potent dose-dependent inhibition pattern. The global nonparametric Friedman test to changes from placebo in 15 objective variables from psychomotor performance showed a significant impairment of similar magnitude after hydroxyzine 25 mg (p = 0.01) and RU 80 mg (p = 0.02), but this was slower in development and recovery after the latter. After RU 40 mg, a smaller impairment was also obtained (p = 0.04). Activity (p = 0.01) and drowsiness (p = 0.02) scales showed significant changes, the subjects feeling less active and more drowsy after all active treatments.

Conclusion: RU presents a potent dose-dependent peripheral anti-H1 activity, displaying psychomotor impairment activity only at the highest dose (80 mg), while therapeutically relevant lower doses (10 and 20 mg) were similar to placebo.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Attention / drug effects
  • Cross-Over Studies
  • Cyproheptadine / analogs & derivatives*
  • Cyproheptadine / pharmacology*
  • Decision Making / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Flicker Fusion / drug effects
  • Follow-Up Studies
  • Histamine / administration & dosage
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Hydroxyzine / pharmacology
  • Male
  • Motor Activity / drug effects
  • Neuropsychological Tests
  • Pain Measurement / methods
  • Platelet Activating Factor / antagonists & inhibitors*
  • Psychomotor Performance / drug effects*
  • Reaction Time / drug effects
  • Self-Assessment
  • Skin Tests / methods*
  • Statistics, Nonparametric
  • Time Factors


  • Histamine H1 Antagonists
  • Platelet Activating Factor
  • rupatadine
  • Cyproheptadine
  • Hydroxyzine
  • Histamine