Abstracts
Tenoxicam, a new non-steroidal anti-inflammatory drug has been compared with piroxicam and indomethacin in a range of pharmacological and biochemical inflammation test systems. In a chronic (17-day) adjuvant arthritis in the rat, tenoxicamand piroxicam were equally effective in reducing several indices of inflammation and were less ulcerogenic and better tolerated than indomethacin. The oxicams reduced the oedematous and cellular components of a carrageenan pleurisy at 4 hours while at 24 hours they increased exudate volume and selectively inhibited the accumulation of mononuclear cells. These agents also reduced the inflammatory component of a delayed hypersensitivity response to methylated bovine resum albumin in the mouse. The oxicams were about 100-fold less active than indomethacin as inhibitors of prostaglandin synthetase but all three compounds reduced about equally the release of prostaglandin E2 from phagocytosing rat PMN and interleukin 1-stimulated human rheumatoid synovial cells. The compounds had no effect on the release of superoxide anion, lysosomal enzymes or collagenase from cultured cells, neither did they inhibit isolated collagenase. Only indomethacin stabilized albumin against heat denaturation.
References
E.H. Wiseman andJ.G. Lombardino,Oxicams — a novel family of non-steroidal anti-inflammatory drugs, Eur. J. Rheumatol. Inflamm.4, 280–297 (1981).
Y. Tanaka, M. Maeda andK. Nakamura,Pharmacological studies on Ro 12-0068, a new non-steroidal anti-inflammatory drug, Folia pharmac. jap.77, 531–532 (1981).
K.M. Strub, L. Aeppli, A. Daum andR.K.M. Müller,Ro 12-0068 — a new non-steroidal anti-inflammatory agent with analgesic properties, XVth Int. Cong. Rheumatol. (Paris) Abstract 376 (1981).
K.M. Strub, L. Aeppli, C.H. Cashin, A. Daum, R.K.M. Müller andK. Nakamura,The pharmacology of the non-steroidal anti-inflammatory drug, tenoxicam. For submission to Arzneimittel-Forsch.
E.F. Valdés, C.A. Barclay andC.A. Traballi,Clinical evaluation of the thienothiazine derivative, Ro 12-0068, in rheumatoid arthritis, Curr. ther. Res.31, 402–407 (1982).
B. Klein,Clinical results with Ro 12-0068 in the treatment of chronic polyarthritis and gout XVth Int. Cong. Rheumatol. (Paris) Abstract 374 (1981).
E.F. Valdés, A.D. Nieri, R. Rodriguez andA. Debian,Experience with the thienothiazine derivative, Ro 12-0068, in rheumatoid arthritis and acute gout, XVth Int. Cong. Rheumatol. (Paris) Abstract 377 (1981).
H.A. Bird, J. Hill, D.B. Galloway, J.S. Dixon andV. Wright,A double-blind comparison of two doses of Ro 12-0068 (Tilcotil) and ibuprofen in rheumatoid arthritis, Xth Eur. Cong. Rheumatol. (Moscow) Abstract 567, (1983).
H. Ott,Clinical trial in osteoarthrosis with Ro 12-0068, a new non-steroidal anti-inflammatory drug, XVth Int. Cong. Rheumatol. (Paris) Abstract 375 (1981).
B. Kirchheiner, P. Holm, E.M. Jensen, J. Kryger, O. Romberg andA. Salveson, A new long-acting anti-inflammatory agent, tenoxicam (TILCOTIL®). InOsteoarthritis of the Knee and the Hip: A Randomised Comparison with Indomethacin, Curr. ther. Res.32, 627–632 (1982).
B.B. Newbould,Chemotherapy of arthritis induced in rats by mycobacterial adjuvant, Br. J. Pharmac.21, 127–136 (1963).
C.H. Cashin, J. Gill, S.A. Jones andA.J. Kennedy,An assessment of the delayed hypersensitivity reaction to methylated bovine serum albumin in the mouse and its use in the evaluation of drug effects on cell-mediated immune reactions Agents and Actions,9, 553–559 (1979).
K.J. Stone, S.J. Mather andP.P. Gibson,Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone, Prostaglandins10, 241–248 (1975).
J.R. Vane,Use of isolated organs for detecting active substances in the circulating blood, Br. J. Pharmac.23, 360–373 (1964).
J.-M. Dayer, S.R. Goldring, D.R. Robinson andS.M. Krane, Cell-cell interactions and collagenase production. InCollagenase in Normal and Pathological Connective Tissue, pp. 83–104. (EdsD.E. Woolley andJ.M. Evanson), 1980.
B. Johnson-Wint,A quantitative collagen film collagenase assay for large numbers of samples, Analyt Biochem.104, 175–181 (1980).
Y. Mizushima,Inhibition of protein denaturation by antirheumatic or antiphlogistic agents, Archs int. Pharmacodyn. Thér.149, 1–7 (1964).
M.B. McGuire, G. Murphy, J.J. Reynolds andR.G.G. Russell,Production of collagenase and inhibitor (TIMP) by normal rheumatoid and osteoarthritic synovium in vitro: effects of hydrocortisone and indomethacin, Clin. Sci.61, 703–710 (1981).
C.E. Brinckerhoff, R.M. McMillan, J.-M. Dayer andE.D. Harris,Inhibition by retinoic acid of collagenase production in rheumatoid synovial cells New Engl. J. Med.303, 432–436 (1980).
J.R. Ward andR.S. Cloud,Comparative effect of antirheumatic drugs on adjuvant-induced polyarthritis in rats. J. Pharmac. exp. Ther.152, 116–121 (1966).
D. Bradshaw, P.H. Franz andS.J. Greenham,Comparative effects of carprofen, benoxaprofen and indomethacin on the development and decay phases of a carrageenan pleurisy in the rat, Agents and Actions14, 667–672 (1984).
I.G. Otterness, D.L. Larson andJ.G. Lombardino.An analysis of piroxicam in rodent models of arthritis, Agents and Actions12, 308–312 (1982).
G.A. Higgs, K.E. Eakins, K.G. Mugridge, S. Moncada andJ.R. Vane,The effects of nonsteroidal anti-inflammatory drugs on leukocyte migration in carrageenin-induced inflammation Eur. J. Pharmac.66, 81–86 (1980).
H.B. Kaplan andH.S. Edelson,Non-steroidal anti-inflammatory agents dissect the sequence of neutrophil (PMN) activation, Clin. Res.29, 675A (1981).
H.S. Edelson, H.B. Kaplan, H.M. Korchak, J.E. Smolen andG. Weissmann,Dissociation by piroxicam of degranulation and superoxide anion generation from decrements in chlortetracycline fluorescence of activated human neutrophils, Biochem. Biophys. Res. Commun.104, 247–253 (1982).
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Bradshaw, D., Cashin, C.H., Kennedy, A.J. et al. Pharmacological and biochemical activities of Tenoxicam (Ro 12-0068), a new non-steroidal anti-inflammatory drug. Agents and Actions 15, 569–577 (1984). https://doi.org/10.1007/BF01966776
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DOI: https://doi.org/10.1007/BF01966776