Effect of SA-103 on experimental allergic models in vivo and in vitro--comparison with disodium cromoglycate.
The anti-allergic action of N-[4-(4-methoxyphenyl)-2-thiazolyl]-1H-tetrazol-5-carboxamide (SA-103) was investigated and compared with that of disodium cromoglycate (DSCG). 1) Oral administration of SA-103 (0.1-10 mg/kg, p.o.) showed dose-dependent inhibition of 48 hr homologous passive cutaneous anaphylaxis (PCA) in rats. The inhibition rate (50%) of the compound at 1 mg/kg was comparable to that of DSCG at 1 mg/kg (i.v.). 2) Both of the drugs concentration-dependently inhibited the release of in vitro anaphylactic histamine from rat peritoneal exudate cells, but SA-103 was 1,000 times as potent as DSCG. 3) High doses (50 and 100 mg/kg, p.o.) of SA-103 tended to suppress 7-day homologous PCA in guinea pigs by only 20-30%. DSCG (100 mg/kg, i.v.) did not influence the reaction. 4) Neither anaphylactic histamine nor leukotriene release from guinea pig lung fragments was markedly influenced by SA-103 (10(-8)-10(-5) g/ml) or DSCG (10(-5)-10(-3) g/ml). 5) The histamine and serotonin induced contractions of the isolated guinea pig ileum were minimally enhanced or suppressed by very high concentrations (10(-4) g/ml) of SA-103 and DSCG. In addition to the above results, prolonged treatment with either compound before antigen challenge decreased the inhibitory response to anaphylactic histamine release from rat peritoneal cells. It is suggested, therefore, that the main mechanism(s) of the anti-allergic action of SA-103 is similar to that of DSCG, and SA-103 may be expected to be effective against allergic diseases.
D000818:Animals; D004205:Cromolyn Sodium / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006967:Hypersensitivity / Q000188:drug therapy* / Q000378:metabolism; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D006633:Histamine Antagonists; D015289:Leukotrienes; D013777:Tetrazoles; D013844:Thiazoles; C077754:SA 103; D004205:Cromolyn Sodium