Evaluation of a modified hexose sugar, amiprilose hydrochloride, in experimental models of synovitis.
Amiprilose HC1 (SM-1213), a nontoxic modified hexose sugar, was evaluated in in vivo and in vitro models of synovitis. In 8 sequential trials, 90 Louvain (LOU) rats and 91 Sprague-Dawley (SD) rats were immunized with chick type II collagen and given amiprilose HC1 in water (1 mg/ml) or water alone. In the LOU rats, the arthritis incidence was 7/46 (15%) in the amiprilose HC1 group vs 16/44 (36%) in the water group (p less than 0.01). In the SD rats, the incidence was 28/46 (60%) in the experimental vs 33/45 (73%) in the control group (p greater than NS), although the prevalence of arthritis on Days 16 and 21 was significantly (p less than 0.03) lower in the experimental group. Amiprilose HC1 did not affect the antibody titers or delayed-type hypersensitivity to collagen, or T cell subset distribution in the LOU experiments. Two analogues, SM-1211 and SM-1212, did not alter this disease. No toxicity was noted. At a nontoxic concentration of 1 mg/ml, amiprilose HC1 suppressed 3H thymidine incorporation in cultured rabbit synovial fibroblasts by 78% and resulted in the appearance of numerous intracytoplasmic granules/vacuoles. These effects were partially antagonized by indomethacin or dexamethasone at 10(-7) M. SM-1211 was inert in this system. Amiprilose HC1 system also reduced rabbit synoviocyte supernatant prostaglandin E2 levels up to 73% in a dose related fashion, but did not affect collagenase activity. These morphologic changes in synoviocytes, combined with anti-inflammatory and antiproliferative effects, provide evidence that amiprilose HC1 possesses modest and nontoxic antirheumatic properties. A search for analogues of this sugar with more substantial clinical activities is warranted.
Kieval
R I
RI
Department of Medicine, Harvard Medical School, Boston, MA.
Young
C T
CT
Prohazka
D
D
Brinckerhoff
C E
CE
Trentham
D E
DE
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003095:Collagen Diseases / Q000188:drug therapy; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012266:Ribose / Q000031:analogs & derivatives; D013585:Synovitis / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000187:drug effects
D000276:Adjuvants, Immunologic; C059520:SM 1212; C059521:3-O-(3-(N',N'-dimethylamino)-n-propyl)glucose; D012266:Ribose; D015232:Dinoprostone; D005944:Glucosamine; C018424:amiprilose