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

Abstract

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.

• Authors: I Yakuo, M Yabuuchi, T Ito
• Journal: Pharmacology & toxicology (Pharmacol Toxicol) Vol. 89 Issue 4 Pg. 171-6 (Oct 2001) ISSN: 0901-9928 [Print] Denmark
• PMID: 11881966 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Butyrophenones
• Histamine H1 Antagonists
• Piperidines
• Receptors, Histamine H1
• Pyrilamine
• ebastine

Topics

• 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)