Histamine1--histamine2 antagonism: effect of combined clemastine and cimetidine pretreatment on allergen and histamine-induced reactions of the guinea pig lung in vivo and in vitro.
In a preliminary study high doses of the H1-antagonist clemastine (clem) and the H2-antagonist cimetidine (cim) were used in order to detect the side effects of both drugs on allergic reactions. After pretreatment with clem or clem/cim different guinea pigs were challenged with either OA or histamine. Bronchial obstruction was measured by body plethysmography using a new parameter ('compressed air'). Pretreatment with clem/cim in high doses protected guinea pigs against OA-induced bronchial obstruction much more effectively than H1-receptor antagonism alone; lower cim doses produced insignificant effects. In histamine-challenged animals cim showed no protective effects. In vitro clem/cim caused a marked reduction of histamine release measured in perfused lungs from 16.9 +/- 4.2 ng/ml (eight control cases) to 2.8 +/- 1.7 ng/ml (n = 8). Our preliminary data suggest that high doses of clem/cim can protect sensitized guinea pigs against allergen-induced bronchial obstruction by inhibiting histamine release.
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D002974:Clemastine / Q000494:pharmacology*; D004347:Drug Interactions; D005122:Exudates and Transudates / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D013997:Time Factors
D000485:Allergens; D006146:Guanidines; D011759:Pyrrolidines; D002927:Cimetidine; D006632:Histamine; D002974:Clemastine