One of the search ways for new medicines is studying fusion compounds´ pharmacological properties among various analogues of well known and widely applied in medicine substances. The piperidine derivatives are of great interest. They are the products of piperidine reduction and are of low toxicological concern as pyridine is a part of many natural complexes (vitamin PP, Vitamin B6, nicotine and others). We have carried out the investigations of new piperidine derivatives synthesized at the Institute of Chemical Sciences named after Berkutov A.B. under the guidance of Academician Praliyev K.D.. The spasmolysants´ primary screening method used is a model of isolated organs. The investigation on small intestine is the most available and, in this connection, very popular method. For the experiment animals of one species, sex, age and body mass (±10%) are selected. The purpose of our work has become the study of biological potency and toxicity of a new piperidine derivatives´ range obtained at the Institute of Chemical Sciences named after Berkutov A.B., the Department of Education and Science of Kazakhstan, under the guidance of a member of the National Academy of Sciences Praliyev K.D.. The antispasmodic activity was investigated on the rats´ small intestine in conditions of calcium and acetylcholine spasm. The work was carried out on the device oriented to the work with isolated organs and manufactured by the Ugo Basile Company, Italy. The acute toxicity was defined by means of a single intraperitoneal introduction of the investigated preparation to white nondescript mice weighing 19-21 g. The evaluation was made according to the LD50 factor. 54 new compounds have been investigated. The research results testify to the presence of antispasmodic activity of the following compounds: NА-281, NА-291, NА-309, NА-310, NА-311, NА-315, NА-320, NА-321, NА-323; the compounds NА-280, NА-294, NА-309, NА-311 blocking calcium spasm and the rest ones - both kinds of spasm. The high antispasmodic activity of the NА-311 and NА-323 compounds, blocking both producing calcium and acetylcholine spasms and with it being of low toxicological concern (NА-311 - 220 mg/kg ± 33,33; NА-323 - 210 mg/kg ± 7,07; the toxicity of no-spa - 213,8 mg/kg +22,61), should be noted.
Conclusions: the piperidine derivatives, being close analogues of the natural compound - pyridine, - are promising for a profound search and development of new low toxicological concern medicines on their basis.
The article is admitted to the International Scientific Conference «Present-day problems of experimental and clinical medicine», Thailand (Bangkok, Pattaya), December 19-27, 2007, came to the editorial office on 12.11.07