A wide spectrum of antiseptic drugs with various effects is used for local treatment of purulent inflammations. Chlorhexidine biogluconate is one of these drugs, however, in addition to the antiseptic effect, it seems to influence the neuromuscular junction activity, which may be important for disease development and should be at least taken into account. It has been previously suggested that chlorhexidine has a channel-blocking effect on a neuromuscular junction [1], although the type and mechanisms of this blockage remain unclear. Therefore, in this study, we analyzed the mechanism underlying the chlorhexidine effect on the receptor-channel complex of the muscle cholinoreceptor.Isolated neuromuscular preparations (sciatic nervetailor's muscle) were obtained from frogs by a previously described standard two-electrode voltage clamp procedure [2]. Under rare electric stimulation (0.05 Hz), chlorhexidine at concentrations of 2-15 µ M caused a concentration-dependent decrease in the amplitude and the time constant of the decline of evoked postsynaptic currents (EPCs). A typical experiment illustrating the effect of 5 µ M chlorhexidine is shown in Fig. 1. It can be seen that the chlorhexidine effect remained almost uninhibited. The Hill constant ( n H = 0.9) and the concentration of the blocking agent that caused a half-maximum effect ( IC 50 = 4.7 µ M at − 70 mV) were determined by approximation of the averaged dose versus effect curves in Hill's equation. With respect to the effect on the amplitude-time parameters, chlorhexidine resembles open channel-blocking agents and substances that accelerate desensitization and enhance the inhibiting effect at increasing frequency of nerve stimulation. Therefore, in a series of experiments, the frequencies of rhythmic muscle stimulation were 10 and 60 Hz. In the control group, the potentiation grew up in a burst of 20 signals with increasing frequency and was estimated as the last-tofirst signal ratio (108.5 ± 7.6% at 10 Hz, 120.5 ± 12% at 60 Hz; n = 6). In a neuromuscular preparation perfused with a 2 µ M chlorhexidine solution, potentiation within a burst was followed by a pronounced depression, which was also more intense at a higher frequency ( 53.2 ± 3 .1% at 10 Hz, 32.6 ± 3 .5% at 60 Hz; n = 4). This is the effect typical of desensitization promoters and open channel-blocking agents. The role of desensitization in chlorhexidine effect was evaluated in experiments with acetylcholine esterase inhibition (before the experiment, the preparations were kept in a 5 µ M armine solution). Under the conditions of choline esterase inhibition and a stimulation frequency of 10 Hz, potentiation ( 151.5 ± 6.2%; n = 6) and depression ( 60.9 ± 10.6%; n = 5) were observed in the control and after addition of 2 µ M chlorhexidine, respectively. Since after choline esterase inhibition, no significant changes were in the degree of depression, chlorhexidine is not presumably a substance that accelerates desensitization.The effect of chlorhexidine on the muscle-type nicotinic cholinergic recep...