SOME ANTIALLERGIC AND ANTIINFLAMMATORY ACTIONS OF 2-N-CARBOXAMIDINONORMIANSERIN (FCC5)

The aims of these studies were to examine the effects of FCC5 (2-carbo xamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2,-a) azepi ne HCl), an analogue of mianserin, on immediate type hypersensitivity reactions in-vitro. The actions of FCC5 were examined on the Schultz-D ale reaction of guinea-pig ileum and on histamine and leukotriene rele ase from human- and guinea-pig-sensitized lung fragments. FCC5 (applie d topically) was assessed for anti-inflammatory activity in-vivo again st phorbol-12-myristate-13-acetate (PMA)induced oedema in the mouse ea r. FCC5 (IC50 = 0.17 mu M) was a potent inhibitor of the Schultz-Dale reaction in-vitro, as assessed by a concentration-dependent attenuatio n of egg albumin-induced contractions of sensitized guinea-pig isolate d ileum. Using human and guinea-pig isolated sensitized lung fragments , FCC5 (1-100 mu M) attenuated antigen-induced release of sulphidopept idoleukotrienes and histamine. FCC5 (50 mu g topically) resembled mian serin and indomethacin in attenuating PMA-induced mouse ear Inflammati on. These properties together with previously published evidence of lo ng lasting antihistamine properties invivo, suggest that FCC5 has ther apeutic potential as an anti-allergic agent, especially in pathologica l conditions where an inflammatory component is present.