The modification by ketotifen of respiratory responses to histamine and antigen in guinea-pigs.

Aerosolized solutions of histamine or ovalbumin were administered to control or ovalbumin-sensitized guinea-pigs. The time to onset of respiratory distress (preconvulsion time) during challenge with these agents was measured using a force-displacement transducer on the animal's back. The preconvulsion time for each guinea-pig was compared with and without ketotifen pretreatment. Ketotifen administered both by aerosol and intraperitoneal injection (i.p.) significantly protected (p less than 0.001) each guinea-pig from the effects of aerosol challenge with histamine. Ovalbumin-sensitized animals were also protected from the effects of antigen aerosol challenge by ketotifen pretreatment. Sodium cromoglycate (DSCG), administered as an aerosol, did not protect sensitized animals from ovalbumin challenge. The Konzett-Rössler technique was used to measure the response to the intravenous injection (i.v.) of histamine in anaesthetized artificially ventilated guinea-pigs. Ketotifen was three times more potent than mepyramine in inhibiting the histamine-induced increase in air overflow volume.