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.
Leitch
I M
IM
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Temple
D M
DM
Wei
H
H
Boura
A L
AL
D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004342:Drug Hypersensitivity / Q000188:drug therapy; D004347:Drug Interactions; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin / Q000008:administration & dosage / Q000633:toxicity; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006634:Histamine H1 Antagonists; D015289:Leukotrienes; D010793:Phthalazines; D012702:Serotonin Antagonists; C075499:2-N-carboxamidinonormianserin; D008803:Mianserin; D010047:Ovalbumin; D013755:Tetradecanoylphorbol Acetate; C020976:azelastine