Studies on a New Antiallergic Pyridinecarboxamide TA-5707F and Its Sodium Salt (TA-5707) I. Inhibition of IGE-lnduced Passive Cutaneous Anaphylaxis (PCA) in Rats

Abstract

Abstract-Effectsof TA-5707F [6-methyl-N-(1H-tetrazol-5-yl)-2-pyridinecarbox amide] 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 I D50, 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 adminis tration 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 I D50) of either drug, but not after oral pretreatment with a therapeutic dose of TA-5707 or TA-5707F.

Studies on a new antiallergic pyridinecarboxamide TA-5707F and its sodium salt (TA-5707). II. Mechanism of antiallergic action of TA-5707.

“…Discussion TA-5707 inhibited the PCA reaction in the rat when administered before the challenge, but it exerts little or no activity when given after the challenge (1). There was mutual cross-tachyphylaxis between the inhibitory actions of TA-5707 and DSCG, when large doses (ca.…”

“…Thus, TA-5707 and TA-5707F [see (1)] are expected to be useful therapeutic agents against allergic diseases in clinical practice.…”

“…In the previous paper, we reported on the PCA-inhibitory activities of a new orally effective antiallergic agent [6-methyl-N (1 H-tetrazol-5-yl)-2-pyridinecarboxamide (TA-5707F) ] and its sodium salt (TA-5707) (1). When administered orally to rats, TA 5707F and TA-5707 were bioequivalent, affording nearly identical time courses of response with a peak at 5 min after adminis tration, and their ID50 values were both about 1 mg/kg.…”

“…250 g) were purchased from Shizuoka Laboratory Animal Center and maintained on laboratory chow before use. The rats were used without fasting , because reproducible antiallergic effects of orally administered TA-5707 or TA-5707F were observed with non-fasted animals as described in the previous study (1).…”