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  • 1
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract AHR-10037 is an anti-inflammatory compound possessing analgesic and antipyretic properties and a high therapeutic index. AHR-10037 was comparable to indomethacin in suppressing acute (Evans blue-carrageenan pleural effusion) and chronic (adjuvant-induced arthritis) inflammation. There was a delayed onset of antipyresis (yeast-induced hyperthermia in rats), analgesia (acetylcholine-induced abdominal constriction in mice) and inhibition of caster oil-induced diarrhea in rats. Antipyresis occurred 3 hours after administration of AHR-10037, 4 mg/kg, PO, vs 1 hour after administration of acetylsalicylic acid, 100 mg/kg, PO; maximum analgesic activity (ED50-4.1 mg/kg) occurred at 4 hours. AHR-10037 was inferior to indomethacin in suppressing castor oil-induced diarrhea in rats. The therapeutic index of AHR-10037 (relating acute anti-inflammatory potency to gastric toxicity potency relative to indomethacin) ranged from 56–91. The pharmacological profile suggests that AHR-10037 is a prodrug convertedin vivo to a cyclooxygenase inhibitor.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Macrophages and monocytes secrete a factor(s) which can stimulate the synthesis of collagenase in synovial cells and in chondrocytes. Incubation of rabbit chondrocytes with macrophage conditioned medium (MCM) and with the calcium channel blockers, nifedipine, verapamil or diltiazem (up to 200 μM) had no effect on collagenase synthesis. However, TMB-8 (8-[N, N-diethylamino]-octyl 3,4,5,-trimethoxybenzoate hydrochloride), an inhibitor of internal calcium movement, did inhibit the process with an IC50 of approximately 130 μM. The calmodulin antagonists, trifluoperazine, chlorpromazine and calmidazolium (R-24571) were effective inhibitors of the process with IC50's of 40 μM, 18 μM and 3.5μM, respectively. Collagenase activity itself was not affected by these agents. The data suggests that calmodulin and/or internal calcium movement may play a role in the macrophage factor-stimulated synthesis of collagenase in rabbit chondrocytes.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bromfenac [2-amino-3-(4-bromobenzoyl) benzeneacetic acid sodium slat sesquihydrate] is an anti-inflammatory/analgesic agent that possesses potent topical activity in rats, guinea pigs, and mice. In rat models of acute (carrageenan paw edema) and chronic (adjuvant arthritis) inflammation, preparations of bromfenac at concentrations as low as 0.01–0.32% (0.01–0.32 mg bromfenac) produced significant anti-inflammatory activity when applied to the injected paw or to the backs of rats. In the acute paw edema test, topical bromfenac was more potent than indomethacin or hydrocortisone and about as active as triamcinolone acetonide. Bromfenac, at concentrations of 0.1–0.32%, showed topical analgesic more potent than indomethacin (24.9×), more potent than ketoprofen (⊂14.9×), and superior to piroxicam. In the guinea pig UV-erythema test, bromfenac was active (26.1×indomethacin) when applied to the UV-exposed site, but not when applied away from the site. The results suggest that bromfenac has activity topically because of a local and a systemic effect. Test results obtained with a long (4–7 hr) pretreatment time (paw edema, adjuvant arthritis, abdominal constriction) are due in great part to a systemic effect of topically applied bromfenac, while the UV-erythema test (1-hr treatment time) clearly indicates a local effect.
    Type of Medium: Electronic Resource
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