A comparison of the in vivo effects of ketotifen, clemastine, chlorpheniramine and sodium cromoglycate on histamine and allergen induced weals in human skin.

Abstract

1 The effect of ketotifen was compared with that of clemastine and chlorpheniramine, known antihistamines, and sodium cromoglycate, a drug considered to have mast cell 'stabilizing' properties on histamine and allergen wealing reactions in human skin, in random order, double-blind, placebo controlled studies. 2 Ketotifen was significantly more potent in the inhibition of both histamine (P < 0.001) and allergen (P < 0.001) skin wealing reactions than either clemastine or chlorpheniramine. Sodium cromoglycate had no significant effect on either histamine or allergen skin wealing reactions in any of the concentrations tested. 3 However ketotifen, like clemastine, had a significantly greater inhibitory effect on histamine than on allergen induced weals (P < 0.001) and both drugs were shown to act as competitive antagonists of histamine. 4 Ketotifen has been shown to be a potent anti-histamine but there is no evidence from these in vivo studies to suggest that it has any additional inhibitory activity on release of mediators from mast cells in human skin.

Histamine and allergen induced changes in nasal airways resistance measured by anterior rhinomanometry: reproducibility of the technique and the effect of topically administered antihistaminic and anti‐ allergic drugs.

“…Indeed we have previously shown that clemastine and ketotifen are more potent antihistamines than chlorpheniramine at least in human skin (Phillips et al, 1983). This is the first study in which ketotifen has been administered topically on to the nasal mucosa.…”

“…This is the first study in which ketotifen has been administered topically on to the nasal mucosa. This drug has been shown to possess powerful antihistaminic effects both in vitro and in vivo (Martin & Roemer, 1978;Phillips et al, 1983). The lack of a significant inhibitory effect of ketotifen against histamine provocation therefore requires explanation.…”

“…This drug is thought to exert its main therapeutic effect in man by mast cell stabilisation (Cox, 1971;Orange et al, 1971), although more recent studies have suggested that it might possess additional properties (Stokes & Morley, 1981). Ketotifen is a benzocyclohepathiophene derivative shown to have antihistaminic properties in man (Martin & Roemer, 1978;Phillips et al, 1983). It is also claimed that this drug might have an anti-allergic effect similar to SCG as it inhibits passive cutaneous anaphylaxis reactions in rats (Martin & Roemer, 1978), though we have been unable to demonstrate any 'anti-allergic' effect of ketotifen in human skin at least after single dose administration (Phillips et al, 1983).…”

“…Ketotifen is a benzocyclohepathiophene derivative shown to have antihistaminic properties in man (Martin & Roemer, 1978;Phillips et al, 1983). It is also claimed that this drug might have an anti-allergic effect similar to SCG as it inhibits passive cutaneous anaphylaxis reactions in rats (Martin & Roemer, 1978), though we have been unable to demonstrate any 'anti-allergic' effect of ketotifen in human skin at least after single dose administration (Phillips et al, 1983). The purpose of this investigation was to measure changes in NAR induced by histamine and allergen by anterior rhinomanometry, to determine their repeatability and reproducibility, and to examine the effect of topically administered clemastine, ketotifen and SCG on these changes.…”

The influence of ranitidine, alone and in combination with clemastine, on histamine‐mediated cutaneous weal and flare reactions in human skin.

“…aneous weal and flare reactions evoked by allergen or compound 48/80 (Marks & Greaves, 1977;Johnson et al, 1984;Smith et al, 1980;Summers et al, 1981). Phillips et al (1983) examined the dose response relationships for H1-receptor inhibition of histamine (and allergen) induced cutaneous weal reactions by studying different concentrations of the H1-receptor antagonists administered intradermally. In order to define more clearly the effect of H2-receptor antagonism on cutaneous reactions mediated by histamine, we have employed a slight modification of the same technique to study the effect of ranitidine, an H2-receptor antagonist of between 4 and 10 times greater potency than cimetidine (Bradshaw et al, 1979;Daly et al, 1979;Brittain et al, 1981), over a 104 fold range of local tissue concentrations.…”