337 Antitussive activity of alcoxyphenyl carbamic acid analogues Jana Jurecekova 1 , Gabriela Nosalova 1,2 , Ludovit Jurecek 1 , Jozef Csollei 3 , Veronika Sivova 1 and Slavomir Nosal 4 1 Biomedical Center Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4D, Martin, Slovakia 2 Department of Pharmacology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4D, Martin, Slovakia 3 Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, Brno, Czech Republic 4 Department of Pediatric Anesthesiology and Intensive Medicine, Jessenius Faculty of Medicine, Comenius University in Bratislava, Kollarova 2, Martin, Slovakia Abstract. In this study we report pharmacological evaluation of four newly synthetized analogues of alcoxyphenyl carbamic acid, structurally related to butamirate citrate that is frequently used as cough suppressing drug, and marked as ATK 231, ATK 241, ATK 251 and ATK 261. Tese agents with various modifcations of the molecular structure have been tested for antitussive activity in cough induced by inhalation of aerosol of citric acid (0.3 M) over 3 minutes using conscious guinea pigs. Results revealed signifcant cough suppressing activity without signifcant infuence on specifc airways resistances in all tested substances. ATK 231 and ATK241 showed signifcantly higher total antitussive activities when compared to both codeine phosphate and butamirate citrate, while ATK 251 only comparing to butamirate citrate. We did not observe any notable adverse efects and these compounds could thus potentially represent promising new non-narcotic antitussives suitable for further studies. Key words: Cough — Citric acid — Guinea pigs — Airways resistance — Antitussive activity Gen. Physiol. Biophys. (2018), 37, 337–343 doi: 10.4149/gpb_2017048 Correspondence to: Slavomir Nosal, Comenius University in Bratislava, Jessenius Faculty of Medicine, Department of Pediat- ric Anesthesiology and Intensive Medicine, Kollarova 2, 036 01 Martin, Slovakia E-mail: snosal@jfmed.uniba.sk Introduction Te therapy of pathological cough refex still remains one of the major unmet medical needs (Dicpinigaitis 2011). Currently, the availability of prescription or over-the- counter medications does not defnitely satisfy the need of clinical practice, although high proportion of patients seeks the health care due to acute or chronic cough. Some efective centrally acting drugs came with serious side efects, while efectiveness of many peripherally acting medications has not been fully confrmed (Young and Smith 2011; Derebery and Dicpinigaiti 2013). Butamirate citrate is currently widely used in clinical practice in adults as well as in children for its cough modulation properties (Schenker 1983; Miko 2005; Molassiotis et al. 2010; Jurica 2013). Cough suppressive activity of butamirate citrate in animal models was described already in animal models several decades ago (Nosal’ova and Strapkova 1986; Szuk et al. 1987). Since then, only a limited number of manuscripts has dealt with this potent cough modulating agent and neither described exact mechanism of its action in details. Generally accepted are its local anesthetic, anti-infamma- tory and spasmolytic properties contributing to its periph- eral cough suppressive activity (Eddy et al. 1969; Calderon et al. 1994; Brown et al. 2004). Some studies found that butamirate binds to the dextromethorphan binding site of sigma receptors and NMDA receptors in guinea pig brain with the high afnity and thus possibly exerting some central antitussive properties (Klein and Musacchio 1989). Butamirate as a 2-(2-diethylaminoethoxy)-ethyl ester is chemically related to oxeladine and pentoxyverine. Pentoxyverine has also been described to act as an agonist