AHR-15010--a novel anti-arthritic agent.
AHR-15010 (3-(2-methoxyphenoxy)-1,2-propanediol bissulphamate ester) is a compound of novel structure that displays anti-arthritic activity in adjuvant arthritis in rats. When given orally from days 18 through day 50, (excluding weekends) after adjuvant injection, AHR-15010, at doses of 3.16 to 100 mg kg-1, produced significant anti-inflammatory activity and reduced the severity of the hind paw joint lesions as monitored by X-ray analysis. AHR-15010, however, has no acute anti-inflammatory activity in the Evans Blue-carrageenan pleural effusion assay in rats, has no analgesic activity in mice, and has no activity in a classic, delayed-type, hypersensitivity assay in mice or in a cotton pellet granuloma test in rats. These data, in conjunction with biochemical data showing that AHR-15010 has no prostaglandin synthetase inhibiting activity suggest that AHR-15010 is an anti-arthritic with a unique mechanism of action. AHR-15010 is a carbonic anhydrase inhibitor. Data are presented that suggest that AHR-15010 and acetazolamide, a prototype carbonic anhydrase inhibitor, may present novel approaches to the treatment of arthritis.
Nolan
J C
JC
A. H. Robins Company, Department of Pharmacology, Richmond, VA 23220.
Walsh
D A
DA
Lo
Y
Y
Gathright
C E
CE
Radvany
C H
CH
Foxwell
M
M
Whitman
L
L
Graff
G
G
Sancilio
L F
LF
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004381:Duodenal Ulcer / Q000139:chemically induced; D004487:Edema / Q000517:prevention & control; D005260:Female; D008297:Male; D051379:Mice; D011409:Propylene Glycols / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects; D013449:Sulfonamides / Q000737:chemistry / Q000627:therapeutic use*
D011409:Propylene Glycols; D013449:Sulfonamides; C067748:AHR 15010