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Abstract

Demonstration of novel anti-arthritic and anti-inflammatory effects of diphosphonates.

C J Dunn, L A Galinet, H Wu, R A Nugent, S T Schlachter, N D Staite, D G Aspar, G A Elliott, N A Essani and N A Rohloff
Journal of Pharmacology and Experimental Therapeutics September 1993, 266 (3) 1691-1698;
C J Dunn
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L A Galinet
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H Wu
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R A Nugent
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S T Schlachter
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N D Staite
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D G Aspar
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G A Elliott
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N A Essani
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N A Rohloff
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Abstract

Diphosphonates (DP) are synthetic pyrophosphates with a P-C-P backbone and are predominantly used for the treatment of bone diseases. Several DP have also been shown to exert significant antiarthritic effects in the rat adjuvant-induced polyarthritis model; however, there is no direct evidence for the anti-inflammatory effects of these compounds. We therefore tested the effects of dichloromethylene diphosphonate on delayed-type hypersensitivity granuloma elicited by s.c. implantation of antigen-soaked hydroxyapatite disks in antigen-sensitized mice. Dichloromethylene diphosphonate induced a dose-related inhibition of the delayed-type hypersensitivity granuloma response (38-64% at 25-100 mg/kg/day s.c. or p.o.); novel DP analogs, U-81581, U-82579 and U-84849 were also effective in the same dose range. In contrast, all DP failed to suppress 24-hr delayed-type hypersensitivity paw edema in mice. In addition to rat adjuvant-induced polyarthritis, mouse antigen-induced erosive arthritis was also significantly suppressed by s.c. administration of all four DP. Toxicity was minimal for each DP (> 600 mg/kg p.o. or s.c.). We conclude that DP represent a novel class of anti-inflammatory agents with excellent therapeutic potential for chronic inflammatory diseases including rheumatoid arthritis.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 266, Issue 3
1 Sep 1993
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Abstract

Demonstration of novel anti-arthritic and anti-inflammatory effects of diphosphonates.

C J Dunn, L A Galinet, H Wu, R A Nugent, S T Schlachter, N D Staite, D G Aspar, G A Elliott, N A Essani and N A Rohloff
Journal of Pharmacology and Experimental Therapeutics September 1, 1993, 266 (3) 1691-1698;

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Abstract

Demonstration of novel anti-arthritic and anti-inflammatory effects of diphosphonates.

C J Dunn, L A Galinet, H Wu, R A Nugent, S T Schlachter, N D Staite, D G Aspar, G A Elliott, N A Essani and N A Rohloff
Journal of Pharmacology and Experimental Therapeutics September 1, 1993, 266 (3) 1691-1698;
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