Local anesthetics (LAs) are drugs that inhibit membrane depolarization by reducing sodium conductance. In addition to the most prominent and well-defined function of LAs described above, numerous studies have shown that LAs possess many other properties, such as anti-inflammatory, anti-arrhythmic or analgesic activities. Furthermore, LAs are structurally similar to histamine H-receptor antagonists. Thus, LAs can be considered antihistaminic drugs. The aim of the present study was to determine and compare the antihistaminic effects of lidocaine derivatives - JCB-1, JCB-2 and JCB-3 - on the isolated guinea pig ileum. Only JCB-1 and JCB-2 at the highest concentration (10 4M) showed the antihistaminic effect. The studied compounds showed a dose-dependent effect. Interestingly, lower concentrations of the studied compounds (10 8M and 10"I0M) caused the opposite effect - increased the contraction of the ileum induced by histamine. These effects necessitate further studies. Nevertheless, this is the first time that JCB compounds have been demonstrated to possess antihistaminic properties.