Researches on the topical activity of benzydamine

Barcellona, P. Scorza; Silvestrini, Bruno

doi:10.1016/0014-2999(68)90069-1

Cited by 27 publications

(11 citation statements)

References 6 publications

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“…More chemically complex indazole derivatives which inhibit lipoxygenase enzyme activity (Foster et al, 1989) or antagonize either leukotriene (Yee et al, 1990) or 5-HT3 (Robertson et al, 1990) receptors have also been synthesized. Perhaps of greater relevance to the present study is benzydamine, an indazole derivative, with pronounced antinociceptive activity which has been recognised for over two decades (Silvestrini et al, 1966;Lisciani et al, 1968). The present study illustrates the antinociceptive effect in the mouse of a series of mono-substituted indazoles.…”

Section: Discussionsupporting

confidence: 50%

Characterization of the novel nitric oxide synthase inhibitor 7‐nitro indazole and related indazoles: antinociceptive and cardiovascular effects

Moore

Wallace

Gaffen

et al. 1993

British J Pharmacology

443

171

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1 7-Nitro indazole (7-NI, 10-50mgkg-'), 6-nitro indazole and indazole (25-100mgkg-') administered i.p. in the mouse produce dose-related antinociception in the late phase of the formalin-induced hindpaw licking and acetic acid-induced abdominal constriction assays. The EDm values (mg kg-') were as follows: 7-NI (27.5 and 22.5), 6-nitro indazole (62.5 and 44.0) and indazole (41.0 and 48.5) in the two assays respectively. 3-Indazolinone, 6 amino indazole and 6-sulphanilimido indazole (all 50 mg kg-') were without effect. With the exception of 5-nitro indazole (50 mg kg-') which produced sedation, none of the other indazole derivates examined caused overt behavioural changes. 2 The antinociceptive effect of 7-NI (25 mg kg-', i.p.) in the late phase of the formalin-induced hindpaw licking assay was partially (46.7 ± 16.2%, n = 18) reversed by pretreatment with L-but not D-arginine (both 50 mg kg', i.p.). 3 The time course of 7-NI induced antinociception in the mouse was correlated with inhibition of brain (cerebellum) nitric oxide synthase (NOS) activity. Maximum antinociceptive activity and NOS inhibition were detected 18-30 min following i.p. administration. In contrast, no antinociceptive effect or inhibition of cerebellar NOS was detected 75 min post-injection. 4 7-NI, 6-nitro indazole, indazole, 3-indazolinone and 6-amino indazole (all 50 mg kg-') failed to influence mean arterial pressure (MAP) over the 45 min after i.p. administration in the anaesthetized mouse. Similarly, 7-NI (25 mg kg-') administered i.v. in the anaesthetized rat did not increase MAP or influence the vasodepressor effect of i.v. injected acetylcholine (ACh) over the same period. 0.06 fLM, n = 6) in phenylephrine-precontracted rabbit aortic rings. 6 These data provide further evidence that antinociception following administration of 7-NI in the mouse results from inhibition of central NOS activity and is not associated with inhibition of in vivo vascular endothelial cells NOS. Accordingly, 7-NI (or a derivative thereof) may provide an alternative approach to the development of novel antinociceptive drugs.

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Section: Discussionsupporting

confidence: 50%

Characterization of the novel nitric oxide synthase inhibitor 7‐nitro indazole and related indazoles: antinociceptive and cardiovascular effects

Moore

Wallace

Gaffen

et al. 1993

British J Pharmacology

443

171

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“…Total tissue concentrations obtained were about 58 ~tmol/L although, as the drug may accumulate in the skin, the concentrations at the inflammatory site may be considerably lower [10]. There is conflicting data concerning the accumulation in inflamed tissues.…”

Section: Pharmacokineticsmentioning

confidence: 85%

Pharmacology of benzydamine

Quane

Graham

Ziegler³

1998

Inflammopharmacol

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Benzydamine is a topical anti-inflammatory drug which is widely available and used topically for the treatment of the mouth. It is also used as a gel for application to inflamed joints. It has physicochemical properties and pharmacological activities which differ markedly from those of the aspirin-line non-steroidal anti-inflammatory drugs. Benzydamine is a weak base unlike the aspirin-like drugs which are acids or metabolized to acids. A major contrast with the aspirin-like drugs is that benzydamine is a weak inhibitor of the synthesis of prostaglandins but it has several properties which may contribute to its anti-inflammatory activity. These properties include inhibition of the synthesis of the inflammatory cytokine, tumour necrosis factor-alpha (EC(50), 25 micromol/L). Inhibition of the oxidative burst of neutrophils occurs under some conditions at concentrations of 30 to 100 micromol/L, concentrations which may be produced within oral tissues after local application. A further activity of benzydamine is a general activity known as membrane stabilization which is demonstrated by several actions including inhibition of granule release from neutrophils at concentrations ranging from 3 to 30 micromol/L and stabilization of lysosomes. Lack of knowledge of the tissue concentrations of benzydamine limit the correlation between pharmacological activities in vitro and in vivo. The concentration of benzydamine in the mouthwash is 4 mmol/L but the concentrations in oral tissues have not been studied adequately. Limited data in the rat indicates that concentrations of benzydamine in oral tissues are approximately 100 micromol/L.

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“…Other activities of benzydamine, e.g. the inhibition of platelet aggregation and a 'membrane-stabilizing' effect are, however, observed at concentrations of 2-8 /~g/ml which correspond to the levels observed in body fluids upon systemic administration of the compound [1,6,7]. The 'membrane-stabilizing' activity of benzydamine, which was demonstrated using isolated rat liver lysosomes [7], suggested that this compound might act by inhibiting the release of enzymes and other mediators from inflammatory phagocytes.…”

Section: Introductionmentioning

confidence: 92%

“…Benzydamine is a weak cyclo-oxygenase inhibitor. It affects prostaglandin synthesis at concentrations which are 20 to 80-fold higher than the plasma levels attained under therapy [1][2][3][4][5]. Other activities of benzydamine, e.g.…”

Section: Introductionmentioning

confidence: 99%

Effect of benzydamine on exocytosis and respiratory burst in human neutrophils and mononuclear phagocytes

et al. 1985

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The effect of benzydamine on stimulus-dependent respiratory burst activity and enzyme release was tested in human neutrophils, monocytes and monocyte-derived macrophages. Established anti-inflammatory compounds, indomethacin, phenylbutazone and bufexamac, were tested for comparison. Care was taken to avoid cytotoxic or cytolytic concentrations of the test compounds, and their effect on release of lactate dehydrogenase was also tested. Release of specific and azurophil granules contents were induced in human neutrophils by A23187, PMA and fMLP with and without cytochalasin B pretreatment. Benzydamine inhibited stimulus-dependent release of vitamin B12-binding proteins, a marker for the specific granules, in a concentration-dependent fashion. By contrast, phenylbutazone and bufexamac were practically inactive. The effect of benzydamine on exocytosis of azurophil granules was tested in cytochalasin B-pretreated neutrophils. Benzydamine, again in contrast to the two reference anti-inflammatory compounds, inhibited release concentration-dependently also under these conditions. The concentration of the compound which inhibited exocytosis by 50% was 30-100 microM in normal and 3-10 microM in cytochalasin B-treated neutrophils. The effect of benzydamine and reference compounds on the respiratory burst was tested by assaying for superoxide formation in neutrophils and H2O2 formation in mononuclear phagocytes. Benzydamine was inactive on neutrophils and inhibited slightly the burst response of monocytes and macrophages. Two reference compounds, bufexamac and phenylbutazone, were generally more active. The strongest inhibitory effect was that of phenylbutazone on fMLP-stimulated cells. Benzydamine lacked activity under these conditions, indicating that it does not bind to the receptor of formylated chemotactic peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

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Researches on the topical activity of benzydamine

Cited by 27 publications

References 6 publications

Characterization of the novel nitric oxide synthase inhibitor 7‐nitro indazole and related indazoles: antinociceptive and cardiovascular effects

Characterization of the novel nitric oxide synthase inhibitor 7‐nitro indazole and related indazoles: antinociceptive and cardiovascular effects

Pharmacology of benzydamine

Effect of benzydamine on exocytosis and respiratory burst in human neutrophils and mononuclear phagocytes

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