Some anti-allergic and anti-inflammatory actions of 2-N-carboxamidinonormianserin (FCC5)

The aims of these studies were to examine the effects of FCC5 (2-carboxamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2,-a) azepine HCl), an analogue of mianserin, on immediate type hypersensitivity reactions in-vitro. The actions of FCC5 were examined on the Schultz-Dale reaction of guinea-pig ileum and on histamine and leukotriene release from human- and guinea-pig-sensitized lung fragments. FCC5 (applied topically) was assessed for anti-inflammatory activity in-vivo against phorbol-12-myristate-13-acetate (PMA)-induced oedema in the mouse ear. FCC5 (IC50 = 0.17 microM) was a potent inhibitor of the Schultz-Dale reaction in-vitro, as assessed by a concentration-dependent attenuation of egg albumin-induced contractions of sensitized guinea-pig isolated ileum. Using human and guinea-pig isolated sensitized lung fragments, FCC5 (1-100 microM) attenuated antigen-induced release of sulphidopeptidoleukotrienes and histamine. FCC5 (50 micrograms topically) resembled mianserin and indomethacin in attenuating PMA-induced mouse ear inflammation. These properties together with previously published evidence of long lasting antihistamine properties in-vivo, suggest that FCC5 has therapeutic potential as an anti-allergic agent, especially in pathological conditions where an inflammatory component is present.