Studies on a new antiallergic pyridinecarboxamide TA-5707F and its sodium salt (TA-5707). I. Inhibition of IgE-induced passive cutaneous anaphylaxis (PCA) in rats.
Effects of TA-5707F [6-methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarboxamide] and its sodium salt (TA-5707) on IgE-induced homologous PCA in rats were investigated. 1. Both TA-5707 and TA-5707F were found to be orally effective inhibitors of rat PCA. Maximum activity by oral administration was obtained when they were administered 5 min before the challenge. Their ID50's under these conditions were both approximately 1 mg/kg. Administration 5 min after the challenge was no longer effective. 2. TA-5707 was also effective by intravenous administration, and its ID50, ca. 0.1 mg/kg, was less than that of disodium cromoglycate (DSCG). 3. The PCA-inhibitory activity of TA-5707 was not affected by adrenalectomy and adrenomedullectomy. 4. Daily administration of TA-5707 or TA-5707F for 8 days did not induce drug tolerance. 5. Tachyphylaxis and cross-tachyphylaxis were observed when the PCA-inhibitory activities of TA-5707 and DSCG were tested after intravenous pretreatment with a large dose (ca. 30 times the ID50) of either drug, but not after oral pretreatment with a therapeutic dose of TA-5707 or TA-5707F.
D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D001200:Ascaris / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000947:Antigens, Helminth; D009536:Niacinamide; D007073:Immunoglobulin E; C040360:6-methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarboxamide