Preclinical comparison of ebastine and other second generation H1-antihistamines.

The present study was performed to compare the properties of ebastine--the long duration of antiallergic effect and less penetration to the CNS--with those of other H1-antihistamines. Passive cutaneous anaphylactic reaction was induced and the dye leakage from the skin measured after oral administration of the various H1-antihistamines in guinea pigs. The H1-antihistamines examined inhibited passive cutaneous anaphylactic reactions, with ED50 values of 1.55-5.77 mg/kg administered orally. Evaluation at doses close to the ED50 values determined that the rank order of the various H1-antihistamines for the duration of antiallergic effects, calculated from the AUC, was as follows: ebastine>cetirizine> or =oxatomide=loratadine=epinastine. The inhibition of [3H]-mepyramine binding to the cortical membrane was examined ex vivo after oral administration of the drugs in rats. Ketotifen as a positive control of sedative antihistamine, oxatomide, cetirizine, ebastine and epinastine dose-dependently inhibited the [3H]-mepyramine binding to rat cortical membranes. However, ebastine and epinastine did not show 50% [3H]-mepyramine binding inhibition even at 100 mg/kg orally In conclusion, ebastine was shown to be a potent and long-lasting H1-antihistamine with less effect to the CNS. Consequently, in conjunction the two experimental models used in this study--passive cutaneous anaphylactic reaction in guinea pigs and ex vivo [3H]-mepyramine binding to rat cortical membrane--may be important to estimate the duration of antiallergic effects of drugs and to detect their sedative effects, which are important indicators in the development of new antiallergic drugs.
AuthorsI Yakuo, M Yabuuchi, T Ito
JournalPharmacology & toxicology (Pharmacol Toxicol) Vol. 89 Issue 4 Pg. 171-6 (Oct 2001) ISSN: 0901-9928 [Print] Denmark
PMID11881966 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Butyrophenones
  • Histamine H1 Antagonists
  • Piperidines
  • Receptors, Histamine H1
  • Pyrilamine
  • ebastine
  • Animals
  • Butyrophenones (pharmacokinetics, pharmacology)
  • Cerebral Cortex (drug effects, metabolism)
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Guinea Pigs
  • Histamine H1 Antagonists (pharmacokinetics, pharmacology)
  • Intracellular Membranes (drug effects, metabolism)
  • Male
  • Passive Cutaneous Anaphylaxis (drug effects, physiology)
  • Piperidines (pharmacokinetics, pharmacology)
  • Pyrilamine (metabolism)
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H1 (metabolism)
  • Skin (drug effects, metabolism)

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