Mechanistic studies on the "bronchosparing" activity of celiprolol, a cardioselective beta-adrenoceptor antagonist.

In some animal models, celiprolol, a cardioselective beta-adrenoceptor antagonist, has been reported to relax bronchial smooth muscle, an activity unique for this class of compound. Mechanistic studies with isolated cat tracheal rings and peripheral lung strips from guinea-pigs indicated that this relaxing activity could not be explained by competitive antagonism of serotonin receptors, beta- or alpha 1-adrenergic receptors, or histamine1-, leukotriene- or prostaglandin F2 alpha-receptors. Furthermore, this activity could not be explained by stimulation of beta-adrenergic or histamine2-receptors, nor can it be explained by a nonselective relaxing activity such as via the inhibition of cyclic nucleotide phosphodiesterases. Serotonin-induced contractions of isolated tracheal rings seem to involve a secondary process which could be the unmasking of alpha 2-adrenoceptors. It is this secondary process which appears to be affected by celiprolol; i.e. celiprolol could be a weak but selective antagonist of alpha 2-adrenoceptors associated with serotonin receptors.