title: Inhibitory effect of methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H-pyrazol o[3, 4-d]pyrimidine-2-carboxylate (AA-2379) on type III allergic (Arthus) reaction.
abstract: Methyl 7-butyl-4,5,6,7-tetrahydro-3-methylamino-4,6-dioxo-5-propyl-2H- pyrazolo[3,4-d]pyrimidine-2-carboxylate (AA-2379), a non-steroidal, non-acidic agent, markedly inhibits type III allergic (Arthus) reaction; the ID50 values of AA-2379 in the rat reversed passive Arthus pleurisy, the rat active Arthus pleurisy, and the reversed passive Arthus reaction in rat skin were 5-10 mg/kg, p.o., and 30 mg/kg of AA-2379 inhibited the active Arthus reaction in rabbit skin by about 50%. Dexamethasone, but not acidic non-steroidal anti-inflammatory drugs and aminopyrine, inhibited the Arthus reaction. The vascular permeability in the reversed passive Arthus pleurisy is enhanced biphasically in the early response mediated by physiologically active amines, prostaglandins, and leukotrienes, and in the late response mediated by complements and polymorphonuclear leukocytes (PMNs). AA-2379 inhibited the late response more potently than the early one. Furthermore, when given after the early response was reduced, AA-2379 obviously inhibited the late response. Rat zymosan-induced paw edema and mouse zymosan-activated serum-induced peritonitis, mediated by complements, were dose-dependently inhibited by AA-2379; the ID50 values were 11.4 and 10.2 mg/kg, p.o., respectively. The results suggest that AA-2379 differs from non-steroidal anti-inflammatory agents in strongly inhibiting the late response of the Arthus reaction, which associated with PMNs.
authors.affiliation: Biology Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Makino
authors.forename: T
authors.initials: T
authors.lastname: Naka
authors.forename: T
authors.initials: T
authors.lastname: Saijo
authors.forename: Y
authors.initials: Y
authors.lastname: Maki
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001183:Arthus Reaction / Q000188:drug therapy / Q000276:immunology*; D002199:Capillary Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D005620:Freund's Adjuvant; D008297:Male; D051379:Mice; D010998:Pleurisy / Q000188:drug therapy; D011743:Pyrimidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011743:Pyrimidines; C058395:AA 2379; D003907:Dexamethasone; D005620:Freund's Adjuvant