[Inhibitory effect of AD-1590, a non-steroidal anti-inflammatory drug, on allergic inflammation in mice and rats].
Effect of AD-1590 on allergic inflammations was investigated. AD-1590 and indomethacin at an oral dosage as high as 32 mg/kg did not show any significant inhibitory activity on rat passive cutaneous anaphylaxis, a type-I allergy, although prednisolone and cyproheptadine produced strong inhibition. Against rat adjuvant arthritis, type-III and -IV allergies, AD-1590 showed potent prophylactic (2 and 4 mg/kg/day) and therapeutic (0.4-1 mg/kg/day) effects when given orally once a day for 3 weeks beginning from just before and for 1 week starting from 14 to 18 days after adjuvant inoculation, respectively; however, its prophylactic and therapeutic potencies were about one-fourth and one-fifth, respectively, that of indomethacin. The arthritis was strongly inhibited with prophylactic treatment of prednisolone (1 mg/kg/day) or cyproheptadine (40 mg/kg/day). On the other hand, prednisolone (ED50 = 0.0119 mg/ear, topical) showed strong activity in inhibiting mouse contact hypersensitivity to oxazolone (ear edema), a type-IV allergy, but cyproheptadine only had weak activity. AD-1590 (0.318 mg/ear) and indomethacin (0.699 mg/ear) produced rather strong inhibition; in particular, AD-1590 produced almost complete inhibition at high dosages, whereas most of the non-steroidal anti-inflammatory drugs (NSAID) tested showed weak inhibition or a partial inhibition of about 50% even at the highest dosage. The oral potency of AD-1590 was about 2 and 100 times those of indomethacin and ibuprofen, respectively. These results demonstrate that in allergic inflammation, the pharmacological properties of AD-1590 are somewhat different from those of other NSAID and different from those of prednisolone and cyproheptadine.
Nakamura
H
H
Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Motoyoshi
S
S
Ishii
K
K
Kadokawa
T
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000517:prevention & control; D003877:Dermatitis, Contact / Q000188:drug therapy; D003990:Dibenzoxepins / Q000494:pharmacology*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003990:Dibenzoxepins; C040006:bermoprofen; D007052:Ibuprofen; D007213:Indomethacin