The Local Anesthetic Activity of 4-(Naphthalen-1-yloxy)but-2-yn-1-yl)-containing Piperidine Derivatives in Experimental Animal Models

Authors : Malika Khaiitova, Yelena Sycheva, Vasılıy Trubachev, Elmıra Satbayeva, Valentına Yu, Talgat Nurgozhın, Edgaras Stankevıčıus, Yeskendir Gassanov, Zauresh Utelbayeva, Khaıdar Tassıbekov

Pages : 465-480

Doi:10.55262/fabadeczacilik.1417891

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Publication Date : 2024-10-23

Article Type : Research Paper

Abstract :Piperidine derivatives are of interest to researchers considering piperidines as an effective scaffold for the synthesis of new compounds. The aim of this research was to investigate the acute toxicity and local anesthetic activity of new synthesized 4-(Naphthalen-1-yloxy)but-2-yn-1-yl)-containing piperidine derivatives. Acute toxicity tests were performed on outbred laboratory mice by subcutaneous injection of increasing concentrations of the test solutions. An initial investigation of local anesthetic activity during infiltration anesthesia was performed on guinea pigs using the Bulbring & Wajda animal model. An in-depth study of the efficacy of the most active compound was performed on a model of infiltration anesthesia of the rabbit’s abdominal wall by determining the threshold of nociception during electrical stimulation. Studied new piperidine derivatives are low-toxic substances, which are confirmed by the results of an acute toxicity study. At the stage of the primary study of local anesthetic activity during infiltration anesthesia on the experimental Bulbring and Wajda model, the LAS-251 compound showed the greatest activity, surpassing the reference drugs in terms of anesthesia index, duration of full anesthesia and total duration of action. At the stage of in-depth study, despite a longer latency period, LAS-251 has a local anesthetic effect longer than procaine and is slightly inferior to lidocaine. Results of present study are promising because complex 1-(4-(naphthalen-1-yloxy)but-2-yn-1-yl)-4-phenylpiperidine (LAS-251) with cyclodextrin showed high local anesthetic activity. This new piperidine derivative is future-oriented for prospective studies of other types of anesthesia, as a potential medicinal substance for therapeutic use in the future.
Keywords : piperidine derivatives, local anesthetic activity, acute toxicity, infiltration anaesthesia