Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes

Abstract

Many antimycotic agents negatively affect the natural immune response. Typically, these drugs impair polymorphonuclear leukocyte (PMN) production of superoxide anion, chemotaxis, or the killing of pathogens.Allylamines are a new class of antimycotic compounds with a new mechanism of antifungal action, i.e., inhibition of the fungal squalene epoxidase. The trial that we describe aimed to evaluate the effects of two allylamines, terbinafine and naftifine, on selected functions of PMNs, i.e., superoxide anion production, chemotaxis, and killing of Candida albicans blastospores. Terbinafine and naftifine on their own did not affect superoxide anion production when they were added to PMNs. When PMNs were preincubated with allylamines and were then stimulated by N-formyl-Met-Leu-Phe or phorbol 12-myristate 13-acetate, superoxide anion production was increased (priming effect). Since intracellular free calcium (Ca2 ,) is involved in the control of superoxide anion production, we evaluated the effects of the allylamines on the Ca2+i concentration ([Ca2+] i).In the presence of terbinafine or naftifine, the [Ca2+]i increased in a dose-dependent manner, the source of Ca2 i was not extracellular since it was not affected by extracellular calcium chelation with ethylene

Scavenging effects of terbinafine on free radicals in vitro

“…On the contrary Vago et al . reported that terbinafine and naftifine, at lower concentrations, did not affect superoxide anion production by PMNs, whereas they could produce a priming effect when the cells were preincubated with 1–100 μmol/L of the allylamine 9 . In both papers, however, a possible effect of the drugs on cell membranes has been suggested.…”

“…Solomon and coworkers reported that naftifine, at concentrations between 30 and 150 g/mL, inhibits polymorphonuclear leucocytes (PMN) chemotaxis chemiluminescence and O 2 ¹ ؒ production, evaluated by the reduction of ferricytochrome C. 8 On the contrary Vago et al reported that terbinafine and naftifine, at lower concentrations, did not affect superoxide anion production by PMNs, whereas they could produce a priming effect when the cells were preincubated with 1-100 mol/L of the allylamine. 9…”

“…The mechanism of action of these compounds seems to be related to a specific inhibition of squalene 2,3-epoxidase (SE), an enzymatic step essential in the synthesis of ergosterol, the main sterol present in fungal membranes. 6,7 The drugs are able to produce in vitro a modification of neutrophil functions with both an increase of superoxide anion production and a reduction of chemiluminescence 8,9 and in vivo an anti-inflammatory activity in animal models or a therapeutic effect in seborrhoeic dermatitis. 10 The aim of our paper was to study the scavenger activity of the allylamine derivative terbinafine in vitro in order to evaluate a possible anti-inflammatory property of the drug.…”

Rationale for selection of a topical antimycotic agent

“…При этом действие нафтифина не при-водит к ослаблению функции неактивированных лейкоцитов. Показано положительное стимулирую-щее действие нафтифина на противогрибковый им-мунный ответ, проявляющийся усилением киллин-га лейкоцитами бластоконидиев C. albicans [19]. В то же время подобное модулирующее действие нафти-фина может быть объяснено снижением степени ад-гезии нейтрофилов к различным субстратам, в част-ности, эндотелию сосудов, что обусловливает про-тивовоспалительную активность нафтифина.…”

Bildung von reaktiven Sauerstoffspezies in vitro durch Malassezia-Hefen

“…Bestimmte MalasseziaAntigene spielen offensichtlich als Allergene eine Rolle als Trigger der Entzün-dungsreaktion beim atopischen Ekzem [24]. Das betrifft eine Reihe von mindestens 12 verschiedenen Antigenen, die bei Bei vorangegangenen In-vitro-Untersuchungen wurde Terbinafin bereits als Sauerstoffradikalfänger erfolgreich eingesetzt [14], es konnte eine Reduktion der ROS-Bildung durch Terbinafin und Naftifin bei Leukozyten gezeigt werden [29,30].…”