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.