The Local Anesthetic Activity of 4-(Naphthalen-1-yloxy)But-2-yn-1- yl)-Containing Piperidine Derivatives in Experimental Animal Models
Khaiitova M. Sycheva Y. Trubachev V. Satbayeva E. Yu V. Nurgozhin T. Stankevičius E. Gassanov Y. Utelbayeva Z. Tassibekov K.
October 2024Society of Pharmaceutical Sciences of Ankara (FABAD)
Fabad Journal of Pharmaceutical Sciences
2024#49Issue 3465 - 480 pp.
Piperidine derivatives are of interest to researchers considering piperidines as an effective scaffold for the synthesis of new compounds. This research aimed to investigate the acute toxicity and local anesthetic activity of new synthesized 4-(Naphthalen-1-yloxy)but-2- yn-1-yl)-containing piperidine derivatives as inclusion complexes with β-cyclodextrin. Moreover, there was hydrogen or 3-methoxyphenyl in position 1 of the substituent at the nitrogen atom of the piperidine ring. The acute toxicity tests were performed on outbred laboratory mice by subcutaneous injection of increasing concentrations of the test solutions. The 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 rabbits abdominal wall by determining the threshold of nociception during electrical stimulation. The new studied 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 the 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. The 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.
acute toxicity , infiltration anesthesia , local anesthetic activity , Piperidine derivatives
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Department of Pharmacology, Faculty of General Medicine-1, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Laboratory of Physiologically Active Compounds chemistry, A.B. Bekturov Institute of Chemical Sciences, Almaty, Kazakhstan
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences, Almaty, Kazakhstan
Institute of Physiology and Pharmacology, Lithuanian University of Health Sciences, Kaunas, Lithuania
Faculty of General Medicine-2, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Department of Pharmacology
Laboratory of Physiologically Active Compounds chemistry
Laboratory of Synthetic and Natural Medicinal Compounds Chemistry
Institute of Physiology and Pharmacology
Faculty of General Medicine-2
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