Bronchodilating activity of mequitazine

The bronchodilating activity of mequitazine (MQ) (10-[3- quinuclidynilmethyl ]-phenothiazine) has been investigated in the guinea-pig using various spasmogens such as acetylcholine, histamine and leukotriene-C4 (LTC4). Mequitazine showed a potent protecting activity versus bronchoconstriction induced by the above agonists and was also able to prevent their capacity to trigger activation of arachidonic acid metabolism and preferential formation of TXA2. The results obtained with the "in vivo" experiments correlate well with those obtained "in vitro" using guinea-pig perfused lungs, where LTC4 and histamine stimulate TXA2 formation and release in the pulmonary effluent. MQ demonstrated its efficacy in protecting passively sensitized guinea-pigs from antigen challenge; this protection is accompanied by a substantial reduction of circulating TXA2. The bronchodilating and antiallergic activity of MQ is likely due to a direct control of histamine and muscarinic receptors and to a diminished bioamplification via eicosanoid activation. In addition, the capacity of MQ to counteract the "in vitro" and "in vivo" effects of LTC4 adds interest to its therapeutic potential.