Dissociation between the anti-anaphylactic and the anti-histaminic actions of ketotifen.

Ketotifen is a compound with strong anti-anaphylactic and anti-histaminic properties both in experimental mental animals and man. In this paper pharmacological experiments are presented which show that these two activities are independent. In the rat, the two actions of ketotifen differ markedly in their time course. The ability of ketotifen to prevent a passive cutaneous anaphylactic reaction is of short duration and is already abolished at times when the compound still fully prevents the cutaneous reaction to histamine. Two anti-histamines, clemastine and mepyramine, were compared with ketotifen. All three compounds prevented the wheal and flare induced by intracutaneous administration of histamine, but only ketotifen also prevented passive cutaneous anaphylaxis. Accordingly, concomitant administration of the anti-histamine clemastine with ketotifen resulted in enhanced histamine-blocking effects but did not influence the anti-anaphylactic action of ketotifen. Finally, clemastine and mepyramine differed from ketotifen in their activities in a model of anaphylactically-induced bronchospasm. Ketotifen prevented the bronchospasm, dyspnea and respiratory arrest in dose-dependent fashion, while the two reference anti-histamines were virtually inactive.