Abstract
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<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.
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References
I. Mota andW. Dias da Silva,The anti-anaphylactic and histamine releasing properties of the antihistamines. Their effect on mast cells, Br. J. Pharmac.15, 396–404 (1960).
U. Martin andD. Romer,The pharmacological properties of a new, orally active anti-anapylactic compound: ketotifen, a benzocycloheptathiophene Arzneim. Forsch.28, 770–782 (1978).
L. Craps, C. Greenwood andP. Radielovic,Clinical investigation of agents with prophylactic anti-allergic effects in bronchial asthma, Clin. Allerg.8, 373–382 (1978).
P. Gobel,The protective effect of ketotifen in bronchial asthma, J. Int. Med. Res.6, 79–85 (1978).
A. Wells andB. Taylor,A Placebo-controlled trial of ketotifen (HC 20511, Sandoz) in allergen induced asthma and comparison with disodium cromoglycate, Clin. Allerg.9, 237–240 (1979).
H. Herxheimer,Repeatable microshocks of constant strength in guinea-pig anaphylaxis, J. Physiol.117, 251–255 (1952).
C. Hamer andD.M. Temple,The effects of indoramin on histamine and antigen-induced changes in respiration in guinea-pigs, Agents and Actions10, 399–402 (1980).
H. Konzett andR. Rössler, Versuchsanordnung zu untersuchingen an der bronchial muskulatur, Naunyn-Schmiedeberg's Arch. Pharmak.195, 71–74 (1940).
O. Arunlakshana andH.O. Schild,Some quantitative uses of drug antagonists, Br. J. Pharmac.14, 48–58 (1978).
J.R. Snapper, P.S. Braasch, S.H. Loring andJ.M. Drazen,In vivo effect of cimetidine on canine pulmonary responsiveness to aerosol histamine, J. Allergy. Clin. Immunol.66, 70–74 (1980).
J.S.G. Cox, J.E. Beach, A.M.J.N. Blair, A.J. Clarke, J. King, T.B. Lee, D.E.E. Loveday, G.F. Moss, T.S.C. Orr, J.T. Tirchie andP. Sheard, Disodium cromoglycate (Intal). In,Advances in Drug Research vol. 5, pp. 115–196. (Eds.M.H. Harper andA.B. Simmonds) Academic Press, London 1970.
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Armour, C., Temple, D.M. The modification by ketotifen of respiratory responses to histamine and antigen in guinea-pigs. Agents and Actions 12, 285–288 (1982). https://doi.org/10.1007/BF01965390
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DOI: https://doi.org/10.1007/BF01965390