Effect of picumast dihydrochloride on antigen-induced early and late airway responses in allergic sheep

In this study the effects of picumast dihydrochloride (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarine++ + dihydrochloride) a novel antiallergic agent, on antigen-induced early and late responses in allergic sheep were examined. For all studies picumast dihydrochloride was administered as an aerosol approximately 20 min before airway challenge with Ascaris suum antigen. Allergic sheep were challenged on four occasions each greater than or equal to 14 days apart: one placebo trial and after 1 mg, 2.5 mg, and 5 mg picumast dihydrochloride aerosol (total dose nebulized). Specific lung resistance (SRL) was used as an index of the airway response to antigen and was measured before and serially after antigen challenge. In the placebo trial (n = 11) antigen challenge resulted in significant early and late airway responses (i.e. 382% and 185% increases in SRL, respectively). Picumast dihydrochloride at 1.0 mg (n = 7) did not protect against the antigen-induced increases in SRL. At 2.5 mg (n = 7), picumast dihydrochloride gave 48% and 55% (both p less than 0.05) protection against the early and late airway responses, respectively. These effects were slightly enhanced with 5 mg picumast dihydrochloride (n = 7) giving 63% protection against the early response and 81% against the late response. These results suggest that the antiallergic agent picumast dihydrochloride may provide some benefit in the treatment of allergic airway disease.