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2 Acta Biologica Cracoviensia. Series Zoologia

2 2012

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Antihistaminic activity of lidocaine derivatives in the isolated guinea pig ileum

100%

Librowski T. , Pytka K. , Salat K. , Rapacz A. , Moniczewski A. , Gdula-Argasinska J. , Tyszka-Czochara M.

tom 54

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.

Influence of gamma-butyrolactone derivatives with analgesic properties on the prostaglandin E2 level and gastric mucosa in rodents

67%

Salat K. , Librowski T. , Gdula-Argasinska J. , Tyszka-Czochara M. , Jastrzebska-Wiesek M. , Moniczewski A. , Rapacz A. , Pytka K. , Filipek B. , Wieckowski K. , Malawska B.

tom 54

Our recent studies indicate that some derivatives of gamma-butyrolactone (GBL) possess analgesic properties in rodent models of pain and inflammation. Despite this pronounced biological activity, the mechanism of action of these GBL still remains unclear. Searching for the plausible mechanism of their action we investigated whether they were (similarly to nonsteroidal anti-inflammatoiy drugs) capable of influencing the PGE2 level in mice subjected experimentally to zymosan-induced peritonitis. The PGE2 level was evaluated in vitro by means of the ELISA assay. We also investigated the influence of orally administered GBL on the rat gastric mucosa in post mortem studies. We have demonstrated that neither of the GBL derivatives influences the PGE2 level in zymosan-induced inflammation of the peritoneal cavity in mice. The investigated compounds are also devoid of adverse effects within the stomach, typical of cyclooxygenase inhibitors, which also indirectly suggests that their analgesic and anti-inflammatory activities result from mechanisms other than cyclooxygenase inhibition.