Benzydamine plays a role in limiting inflammatory pain induced by neuronal sensitization.

Benzydamine is an active pharmaceutical compound used in the oral care pharmaceutical preparation as NSAID. Beside from its anti-inflammatory action, benzydamine local application effectively reliefs pain showing analgesic and anaesthetic properties. Benzydamine mechanism of action has been characterized on inflammatory cell types and mediators highlighting its capacity to inhibit pro-inflammatory mediators' synthesis and release. On the other hand, the role of benzydamine as neuronal excitability modulator has not yet fully explored. Thus, we studied benzydamine's effect over primary cultured DRG nociceptors excitability and after acute and chronic inflammatory sensitization, as a model to evaluate relative nociceptive response. Benzydamine demonstrated to effectively inhibit neuronal basal excitability reducing its firing frequency and increasing rheobase and afterhyperpolarization amplitude. Its effect was time and dose-dependent. At higher doses, benzydamine induced changes in action potential wavelength, decreasing its height and slightly increasing its duration. Moreover, the compound reduced neuronal acute and chronic inflammatory sensitization. It inhibited neuronal excitability mediated either by an inflammatory cocktail, acidic pH or high external KCl. Notably, higher potency was evidenced under inflammatory sensitized conditions. This effect could be explained either by modulation of inflammatory and/or neuronal sensitizing signalling cascades or by direct modulation of proalgesic and action potential firing initiating ion channels. Apparently, the compound inhibited Nav1.8 channel but had no effect over Kv7.2, Kv7.3, TRPV1 and TRPA1. In conclusion, the obtained results strengthen the analgesic and anti-inflammatory effect of benzydamine, highlighting its mode of action on local pain and inflammatory signalling.

Effects of benzydamine and mouthwashes containing benzydamine on Candida albicans adhesion, biofilm formation, regrowth, and persistence.

OBJECTIVES: To assess the effects of benzydamine and mouthwashes (MoWs) containing benzydamine on different stages of Candida albicans biofilm: adhesion, formation, persistence, and regrowth (if perturbed). MATERIALS AND METHODS: C. albicans CA1398, carrying the bioluminescence ACT1p-gLUC59 fusion product, was employed. Fungal cells were exposed for 1', 5', or 15' to 4 different benzydamine concentrations (0.075 to 0.6%) to 2 mouthwashes (MoWs) containing benzydamine and to a placebo MoW (without benzydamine). Treated cells were tested for adhesion (90 min) and biofilm formation (24-h assay). Next, 24- and 48-h-old biofilms were exposed to benzydamine and MoWs to assess regrowth and persistence, respectively. The effects of benzydamine, MoWs containing benzydamine, and placebo on different biofilm stages were quantified by bioluminescence assay and by the production of quorum sensing (QS) molecules. RESULTS: Benzydamine and MoWs containing benzydamine impaired C. albicans ability to adhere and form biofilm, counteracted C. albicans persistence and regrowth, and impaired a 48-h-old biofilm. Some of these effects paralleled with alterations in QS molecule secretion. CONCLUSIONS: Our results show for the first time that benzydamine and MoWs containing benzydamine impair C. albicans capacity to form biofilm and counteract biofilm persistence and regrowth. CLINICAL RELEVANCE: Benzydamine and MoWs containing benzydamine capacity to affect C. albicans biofilm provides an interesting tool to prevent and treat oral candidiasis. Likely, restraining C. albicans colonization through daily oral hygiene may counteract colonization and persistence by other critical oral pathogens, such as Streptococcus mutans, whose increased virulence has been linked to the presence of C. albicans biofilm.

Functional assessment of rat pulmonary flavin-containing monooxygenase activity.

The expression of flavin-containing monooxygenase (FMO) varies extensively between human and commonly used preclinical species such as rat and mouse. The aim of this study was to investigate the pulmonary FMO activity in rat using benzydamine. Furthermore, the contribution of rat lung to the clearance of benzydamine was investigated using an in vivo pulmonary extraction model. Benzydamine N-oxygenation was observed in lung microsomes and lung slices. Thermal inactivation of FMO and CYP inhibition suggested that rat pulmonary N-oxygenation is predominantly FMO mediated while any contribution from CYPs is negligible. The predicted lung clearance (CLlung) estimated from microsomes and slices was 16 ± 0.6 and 2.1 ± 0.3 mL/min/kg, respectively. The results from in vivo pulmonary extraction indicated no pulmonary extraction following intravenous and intra-arterial dosing to rats. Interestingly, the predicted CLlung using rat lung microsomes corresponded to approximately 35% of rat CLliver suggesting that the lung makes a smaller contribution to the whole body clearance of benzydamine. Although benzydamine clearance in rat appears to be predominantly mediated by hepatic metabolism, the data suggest that the lung may also make a smaller contribution to its whole body clearance.

Oral Health-Related Quality of Life and the Use of Oral and Topical Nonsteroidal Anti-Inflammatory Drugs for Pericoronitis.

BACKGROUND Pericoronitis is inflammation of the tissue surrounding a third molar, or wisdom tooth. This study aimed to evaluate the effects of oral and topical analgesic nonsteroidal anti-inflammatory drugs (NSAIDs) on oral health-related quality of life (OHQoL), in terms of oral health and lifestyle, in patients with symptomatic pericoronitis. MATERIAL AND METHODS The study included 60 patients who presented with pericoronitis and who did not undergo surgery within the following seven days. The patients were randomly assigned to three groups and were treated with oral diclofenac (N=20), oral flurbiprofen (N=20), and topical benzydamine (N=20). OHQoL was assessed for all study participants with a self-reported eight-item scale that was developed to evaluate pericoronitis. The total OHQoL scores were calculated for each day during the seven-day study period. RESULTS The study group treated with topical benzydamine had a significantly greater improvement in the OHQoL scores compared with the oral diclofenac and oral flurbiprofen groups on the first four days. Comparison of patients treated with diclofenac and flurbiprofen showed no significant differences for all seven days. A significant initial improvement in OHQoL was found on day 1 for the benzydamine group, on day 2 for the flurbiprofen group, and day 3 for the diclofenac group. CONCLUSIONS In this study, topical benzydamine was found to be a more effective alternative to oral NSAID analgesics, diclofenac and flurbiprofen, in improving OHQoL in patients with pericoronitis.

Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis.

PURPOSE: The purpose of the study is to compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemoradiation-induced oral mucositis in head and neck cancer patients. METHODS: Sixty locally advanced head and neck cancer patients treated with high-dose radiotherapy concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to 2 weeks after the completion of treatment. The total score for mucositis, based on the Oral Mucositis Assessment Scale (OMAS), was used for the assessment, conducted weekly during the treatment period and at the fourth week of the follow-up. Pain score, all prescribed medications, and tube feeding needs were also recorded and compared. RESULTS: The median of total OMAS score was statistically significant lower in patients who received benzydamine HCl during concurrent chemo-radiotherapy (CCRT) than in those who received sodium bicarbonate, (p value < 0.001). There was no difference in median pain score, (p value = 0.52). Nineteen percent of patients in sodium bicarbonate arm needed oral antifungal agents whereas none in the benzydamine HCl arm required such medications, (p value = 0.06). Tube feeding needs and the compliance of CCRT were not different between the two study arms. CONCLUSIONS: For patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy, using benzydamine HCl mouthwash as a preventive approach was superior to basic oral care using sodium bicarbonate mouthwash in terms of reducing the severity of oral mucositis and encouraging trend for the less need of oral antifungal drugs.

Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action.

Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self-administration. Furthermore, BZY-induced Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus accumbens circuitry were significantly reduced in the presence of the CB1 receptor antagonist AM251. These findings provide firm evidence of the abuse liability of BZY and suggest a possible cannabinoidergic mechanism of action. Further research is needed in order to give insights into the molecular mechanism underlying BZY psychoactive and reinforcing effects, to better understand its abuse potential.

IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride, benzydamine hydrochloride with chitosan, calcium hydroxide and chlorhexidine medicaments: An ELISA study.

The aim of the present study was to evaluate IL-1ß, IL-6 and TNF-α expression levels of macrophage cells induced by benzydamine hydrochloride (BNZ), BNZ with chitosan, calcium hydroxide (CH) and chlorhexidine (CHX) medicaments. Half maximal inhibitory concentrations (IC50) were assessed on THP-1, Saos-2, and CRL-2014 cells using MTT assay. THP-1 cells were differentiated into macrophages with phorbol12-myristate13-acetate and activated with lipopolysaccharide. IL-1ß, IL-6 and TNF-α levels in supernatants were determined using enzyme-linked immunosorbent assay (ELISA). The data were examined with one-way ANOVA and Tukey's multiple comparison test (p=0.05). At the selected concentrations, the cell viability was higher than 50% for chitosan and CH, whereas CHX presented lower IC50 values than BNZ and BNZ+chitosan. According to ELISA results, the lowest IL-1ß, IL-6 and TNF-α values were observed with BNZ+Chitosan 50 µg/mL and BNZ 50 µg/mL. BNZ+chitosan 50 µg/mL combination has revealed promising anti-inflammatory effects. Nevertheless, these findings need to be examined in clinical conditions.

Reversion of antibiotic resistance in multidrug-resistant pathogens using non-antibiotic pharmaceutical benzydamine.

Antimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimens. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing drugs as potent antibiotic adjuvants offers a cost-effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug-resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad-spectrum antibiotic-tetracyclines activity against a panel of clinically important pathogens, including MRSA, VRE, MCRPEC and tet(X)-positive Gram-negative bacteria. Mechanistic studies showed that benzydamine dissipated membrane potential (▵Ψ) in both Gram-positive and Gram-negative bacteria, which in turn upregulated the transmembrane proton gradient (▵pH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system-mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline-benzydamine combination against different metabolic states of bacteria involve persister cells. As a proof-of-concept, the in vivo efficacy of this drug combination was evidenced in multiple animal infection models. These findings indicate that benzydamine is a potential tetracyclines adjuvant to address life-threatening infections by MDR bacteria.

An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium.

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1-physiological saline 0.9%; Group No. 2-safflower oil 100 mg/kg; Group No. 3-safflower oil 300 mg/kg; Group No. 4-benzydamine HCl 30 mg/kg; Group No. 5-benzydamine HCl 100 mg/kg; and Group No. 6-naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7-10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7-physiological saline 0.9%; Group No. 8-safflower oil 300 mg/kg; Group No. 9-benzydamine HCl 100 mg/kg; and Group No. 10-naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro-Wilk, Kruskal-Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic-anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

Uncoupled human flavin-containing monooxygenase 3 releases superoxide radical in addition to hydrogen peroxide.

Human flavin-containing monooxygenase 3 (hFMO3) is a drug-metabolizing enzyme capable of performing N- or S-oxidation using the C4a-hydroperoxy intermediate. In this work, we employ both wild type hFMO3 as well as an active site polymorphic variant (N61S) to unravel the uncoupling reactions in the catalytic cycle of this enzyme. We demonstrate that in addition to H2O2 this enzyme also produces superoxide anion radicals as its uncoupling products. The level of uncoupling was found to vary between 50 and 70% (WT) and 90-98% (N61S) for incubations with NADPH and benzydamine over a period of 5 or 20 min, respectively. For the first time, we were able to follow the production of the superoxide radical in hFMO3, which was found to account for 13-18% of the total uncoupling of this human enzyme. Moreover, measurements in the presence or absence of the substrate show that the substrate lowers the level of uncoupling only related to the H2O2 and not the superoxide radical. This is consistent with the entry point of the substrate in this enzyme's catalytic cycle. These findings highlight the importance of the involvement of hFMO3 in the production of radicals in the endoplasmic reticulum, as well as the relevance of single-nucleotide polymorphism leading to deleterious effects of oxidative stress.

Effect of econazole and benzydamine on sensory neurons in culture.

Econazole is an anti-mycotic agent widely used for the treatment of cutaneous fungal infections, and for the therapy of vaginal candidiasis. Topical application of this azole is generally safe, although some patients have complained of mild burning sensation/cutaneous irritation and itching, especially when administered intravaginally. The underlying mechanisms responsible of these adverse effects are poorly understood, though they suggest excitation of cutaneous nociceptor terminals. We report that exposure of primary cultures of rat nociceptors to econazole augments neuronal excitability. This effect appears mediated by increments in the intracellular Ca2+ by stimulating Ca2+ entry and release from the endoplasmic reticulum. Ca2+ entry was not due to activation of thermo transient receptor potential (TRP) channels, suggesting a different ion channel targeted by the azole. Noteworthy, econazole-evoked responses were potentiated by a pro-inflammatory agent, which resulted in an increase in neuronal excitability. Econazole-elicited action potential firing was significantly abolished by the inflammatory cytokine inhibiting drug benzydamine via blockade of voltage-gated Na+ (Nav) channels. Collectively, our results indicate that the burning sensation of econazole is due at least in part to modulation of nociceptor excitability, and such sensation is increased in the presence of pro-inflammatory stimuli and blocked by benzydamine. These findings imply that a combination of the azole with benzydamine has the potential to reduce significantly the unpleasant symptoms related to infection and to the adverse effects of topical econazole formulations.

Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists.

1. The present study was aimed to investigate the effect of benzydamine, an anti-inflammatory drug devoid of activity on arachidonic acid metabolism, on monocyte chemotaxis and to define the possible biochemical correlates of activity. 2. Benzydamine inhibited monocyte chemotaxis in response to three classes of chemoattractants: the prototypic CC-chemokine CCL2 (MCP-1), the microbial product fMLP and the complement cascade component C5a. The effect was dose-dependent with IC50's of 100, 50 and 45 microm for MCP-1/CCL2, fMLP and C5a, respectively. At the dose of 100 microm, the effect resulted in a 50+/-10% inhibition of MCP-1/CCL2-induced chemotaxis and 53+/-6 and 54+/-5% inhibitions of chemotaxis in response of fMLP and C5a, respectively (n=3). 3. Receptor expression as well as calcium fluxes in response to chemoattractants were not affected by benzydamine. 4. Benzydamine strongly inhibited chemoattractant-induced activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and of its upstream activator kinase MEK1/2. ERK1/12 activation in response to chemoattractants was 89-98% inhibited by a 100 microm concentration of benzydamine with an IC50 of 30 microm. 5. Under the same experimental conditions, pretreatment with 100 microm benzydamine caused a 75-89% inhibition of p38 activation (IC50 25 microm). 6. These results indicate that the anti-inflammatory activity of benzydamine is exerted at multiple levels, including monocyte migration to chemotactic factors associated to a blockage of ERK and p38 MAPK pathways.

Effect of inhibitors of prostaglandin synthesis and metabolism on ovum transport in the rabbit.

Several drugs known to affect prostaglandin synthesis, release, or metabolism have been tested for their effects on ovum transport in the rabbit after systemic or local administration. Acceleration of transport was obtained with several drugs; among the most effective were benzydamine, a blocker of thromboxane production, and L11204, an inhibitor of prostaglandin metabolism.

Photoproducts of benzydamine and azapropazone: demonstration of their phototoxicity in vitro.

Red blood cell lysis, photosensitized by the products of the aerobic photolysis of benzydamine (1) and azapropazone (4), was investigated. Irradiation of a methanol solution of 1 and 4 under oxygen produces the photoproducts 3-hydroxy-benzydamine, (2), 2-(3-dimethylaminopropyl)-1-benzylindazolin-3-one (3) and 3-dimethylamino-7-methyl-1,2,4-benzotriazine (5). The mechanism of the photodegradation of 1 was examined. Photoproducts 3 and 5 produce singlet oxygen as demonstrated by trapping with 2,5-dimethylfuran. The photohemolysis rate for the photoproducts 3 and 5 was enhanced by deuterium oxide and oxygen. No change was observed in the presence of reduced glutathione. The photohemolysis rate was low under anaerobic conditions.

Effects of proprietary oral rinses containing chlorhexidine, hexetidine and benzydamine on the proliferation of human buccal epithelial cells in culture.

Cell cultures were established from small samples of buccal tissue, using a 3T3 fibroblast feeder-layer technique. After exposure to increasing dilutions of three proprietary oral rinses for 22 h or 2 h, the effects upon cell proliferation were studied by measurement of [3H]-thymidine incorporation into cellular DNA. Cell membrane damage was assessed by measurement of lactate dehydrogenase content. Cultures exposed to hexetidine-containing or chlorhexidine-containing rinses for 22 h at dilutions of 250-fold or lower showed almost complete inhibition of [3H]-thymidine incorporation. Cultures treated with benzydamine-containing rinse at the same dilutions showed no significant inhibition of incorporation. Exposure to the same dilutions of hexetidine- and chlorhexidine-containing rinses for 2 h resulted in 65% and 20% inhibition of incorporation, respectively. Lactate dehydrogenase content decreased to negligible levels after exposure to the rinse containing hexetidine at a 250-fold dilution, but was unaffected by the other two rinses. Thus dividing buccal epithelial cells in vitro may be adversely affected by exposure to certain commercial oral rinses.

Evidence from two classic irritation tests for an anti-inflammatory action of a natural extract, Echinacina B.

The roots of Echinacea angustifolia (fam. Compositae) were used to obtain an antiphlogistic, immunostimulating and skin repairing extract. On the basis of these potential actions, the extract is used in cosmetic preparations. The aim of this study was to evaluate the anti-inflammatory activity of the extract using different irritation tests. The irritation reaction was induced by application of 0.015 ml of 0.25% croton oil in water to the ears of mice. The raw extract (Echinacina B), topically applied, inhibited oedema both at the maximum (6 hr) and in the decreasing phase (18 hr), and this effect was directly proportional to the doses used. Echinacina B was found to be more potent than the positive control, benzidamine, a topical non-steroidal anti-inflammatory drug. In addition, the extract given iv 1 hr before injection of 0.05 ml of 1% carrageenan into the hind paws of rats inhibited oedema in the histaminic and in the later phases of the phlogistic process. These data show the qualitative value of irritation tests for studying the anti-inflammatory action of a natural plant extract.

Antimicrobial activity of benzydamine, a non-steroid anti-inflammatory agent.

The antimicrobial activity of benzydamine (BD), a non-steroid anti-inflammatory agent, was studied using different techniques against 38 strains belonging to 12 microbial species comprising bacteria, yeasts and a fungus. The minimum inhibitory concentrations, minimum lethal concentrations, per cent survivors after 30-minute exposure to BD (0.1%), growth curves of 7 selected organisms in subinhibitory BD concentrations and killing times for clinical isolates at different BD levels (0.05-0.15%) were determined. The data obtained throughout this study show that BD is a general antimicrobial agent with a rapid biocidal activity against a variety of organisms at concentrations less than those advocated for treatment of inflammatory conditions.

Benzydamine, an unique model of anti-inflammatory activity.

Benzydamine is an anti-inflammatory drug with unique medical uses, namely the topical treatment of oro-pharyngeal and gynaecological conditions. This paper illustrates the rationale for the medical use of benzydamine. Its differences from aspirin-like drugs are pointed out, and evidence is presented that benzydamine does not primarily affect the PGs system, but rather reduces the cell response to injury.

Review of pharmacological data on benzydamine.

Pharmacological results are reviewed supporting the use of benzydamine in so-called "primary inflammations" rather than in rheumatic diseases. In experimental studies, benzydamine shares with aspirin-like drugs their activity in acute inflammatory responses but not in Freund's adjuvant arthritis. The efficacy of benzydamine is mainly manifested against phenomena such as pain and oedema which depend on local mechanisms in the inflammatory focus. Other manifestations such as hyperthermia which are indicative of systemic functional involvement, are poorly affected by the drug. Benzydamine also lacks some of the typical side-effects of aspirin-like drugs which are thought to reflect their generalized activity. Finally topical application increases the analgesic and antiinflammatory activities of benzydamine much more than those of other antiinflammatory drugs. The data reported demonstrate that benzydamine specifically acts on the local mechanisms of inflammation. In order to explain this feature the chemical, pharmacokinetic and biochemical properties of benzydamine are discussed.

Aspects of the mechanisms of action of benzydamine.

Benzydamine shows some properties that are common with other nonsteroidal antiinflammatory drugs (NSAIDs) but displays also properties which are different from those of other NSAIDs. It inhibits prostaglandin and thromboxane biosynthesis at high concentrations, which however can be reached by topical application of the drug. It has no inhibiting effect on amino-acid decarboxylases, which are inhibited by various NSAIDs. Benzydamine has no effect on sulphydryl-group reactivity, contrary to most NSAIDs. It inhibits platelet aggregation and the inhibition of the collagen-induced aggregation appears to be rather selective with respect to other NSAIDs. It displays a stabilizing effect on erythrocyte membranes which appears related to its high affinity for membranes in general, and it inhibits the respiratory burst of stimulated human monocytes and granule enzyme release by human neutrophils.