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Journal of Pharmacology And Experimental Therapeutics, Vol. 179, Issue 1, 114-123, 1971
Copyright © 1971 by American Society for Pharmacology and Experimental Therapeutics

ANTI-INFLAMMATORY AND ANALGETIC PROPERTIES OF d-2-(6'-METHOXY-2'-NAPHTHYL)-PROPIONIC ACID (NAPROXEN)

ADOLPH P. ROSZKOWSKI 1, WENDELL H. ROOKS II 1, ALBERT J. TOMOLONIS 1, and LOIS M. MILLER 1

1 Departments of Pharmacology and Bioassay, Syntex Research, Palo Alto, California

Naproxen displayed marked anti-inflammatory effects. Orally in rats, naproxen (N), indomethacin (I) and aspirin (A) were respectively 11, 16 and 0.2 times as active as phenylbutazone (P) in inhibiting carrageenan-induced paw edema. N reduced granuloma formation around s.c. implanted cotton pellets at dose levels ranging from 3.3 to 20 mg/kg/day without impairing growth in rats. Other agents produced significant effects at the following milligram per kilogram per day dose levels: I, 1 to 2; hydrocortisone, 20; mefenamic acid, 20 to 80; P, 40. Granuloma formation was also reduced by N in adrenalectomized rats. This, lack of thymolytic activity and the finding that N was topically active in reducing croton oil rat ear edema suggest a direct action at inflamed sites and not onevia a corticoid intermediary. With the use of writhing in mice for analgesia appraisal, N, I and P, given p.o., were respectively 7, 60 and 0.8 times as active as A. The same order was maintained with the "Randall-Selitto" analgetic method in rats. A significant rise in pain threshold was obtained at the following p.o. milligram per kilogram dose levels: 1, 3 to 8; N, 25 to 33; mefenamic acid, 30; P, 90; and A, 200 to 300. Similar results were obtained when carrageenan- rather than yeast-provoked pain was used. N, I and P also inhibited yeast-induced pyresis in rats. These were respectively 22, 18 and 3 times as potent as A. All of the compounds except hydrocortisone were acutely "ulcerogenic" in starved rats. This action paralleled the anti-inflammatory action of all agents other tha n A, which was more ulcerogenic p.o.

Submitted on September 8, 1970
Accepted on June 21, 1971




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Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics.