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93. Kallio H., Uusitalo R.J., Maunuksela E.L. Topical anesthesia with or without propofol sedation versus retrobulbar /peribulbar anesthesia for cataract extraction: prospective randomized trial. // J.C.R.S. 2001. - V.27, N.10. -P. 1643-1650.
4. Karp C.L., Cox T.A., Wagoner M.D. et al. Intracameral anesthesia: a report by American Academy of ophthalmology.// Ophthalmology 2001.-V.108, N.9.-P. 1704-1710.
5. Kim S., Yang Y., Kim J. Tolerance of patients and postoperative result: topical anesthesia for strabismus surgery. // J. Pediatr. Ophthalmol. Strabismus. 2000. - V.37, N.6. - P.344-348.
6. Осипова Н.М., Новиков Г.А., Петрова В.В. и др. Опиатные и опиоидные анальгетики в лечении острого и хронического болевого синдрома // Синтез, фармакология и клинические аспекты новых обезболивающих средств - Тезисы докладов Всесоюзной конференции -Новгород - 1991, с.140
7. Пралиев К.Д., Ю В.К., Фомичева Е.Е. и др. Производные пиперидина: взаимосвязь структуры с обезболивающей активностью // Синтез, фармакология и клинические аспекты новых обезболивающих средств - Тезисы докладов Всесоюзной конференции - Новгород -1991, с.106
8. Yepez J., Cedeno de Yepez J., Averalo J.F. Topical anesthesia for phacoemulsification, intraocular lens implantation and posterior vitrectomy. // J. Cataract Refract. Surg.-2003. V.26, N.4. -P.475.
9. Шайда Л.П., Лампусова В.Б., Стягайло C.B. Клиническая фармакология средств для обезболивания стоматологических вмешательств // Эндодонтия today. - 2002. - № 3-4. - С. 79-93.
10. Лампусова В.Б., Проблема недостаточной эффективности местного обезболивания в клинике терапевтической стоматологии // Стоматология. - 2006. - Т. 85, № 6. - С.6-10.
11. Стягайло C.B. Оценка эффективности местного инъекционного обезболивания в зависимости от стоматологической патологии и групповой принадлежности зуба // Стоматологический журнал. - 2007. -№2.-С. 61-62.
12. Стягайло C.B. Эффективность местной анестезии современными анестетиками при лечении пульпита и кариеса // Клиническая медицина. Вопросы клиники, диагностики, профилактики и лечения. Том 15. -Великий Новгород - Алматы, 2007. - С. 373-380.
LOCAL ANESTHETIC ACTIVITY NEW SYNTHETISED PYRIDINE DERIVATIVES BY THE CONDUCTION
ANESTHESIA
Smagulova. G. S., Kim 1.1., Kadirova D. M., students: Erbolatova A. E. Almagalieva B. I.
KazNMUnamed by S. D.Asfendiyarov, Almaty, Kazakhstan
Abstract. Elimination and prevention ofpain is an actual problem of practical medicine. One of the most important directions in solving this problem is the creation of medicinal preparations that have an anesthetic effect. This is due to the fact that the most used anesthetics in the practical medicine exhibit a short-term period of pharmacological action. The numbers of organic compounds that can be used for the synthesis of local anesthetics piperidine derivatives are more interest, including the identified substances that have a pronounced local anesthetic effect. Therefore, the aim of this study was to survey local anesthetic agents among the newly synthesized derivatives of piperidine.
The purpose of this work. The search for compounds having certain advantages over existing local anesthetics in terms of duration of action, potency and toxicity on the model of conduction anesthesia.
Materials and methods of research. In the laboratory of chemistry of synthetic and natural medicinal substances JSC "Institute of Chemical Sciences" named A.B. Bekturov new compounds of piperidine derivatives under laboratory code MAV (local anesthetic substance): MAV-178, MAV-184, MAV-185 were synthesized. Experiments to study the conduction anesthesia been tested on rats by the modified method «tail flick». Determined: duration of total anesthesia and the total duration of the action. The activity of compounds and reference drugs was studied in a 1% solution. Each series of experiments carried out on animals. As a reference preparations were used novocaine, lidocaine and trimecaine.
The modified method of "tail-flick" of rats.
Tail flick method has been developed at the Department of Pharmacology of the St. Petersburg Medical University named after academician I.P. Pavlov. It allows determining the speed of the onset of anesthesia, its depth, duration of complete anesthesia and the total duration of the anesthetic action of preparation.
The activity of compounds and reference preparations was studied in a 0.1% solution. Research was conducted on mongrel white male rats, weighing 200-250 grams.
The principle of the method is to record the latent period of tail-flick in the thermal impact on the middle part focused beam of light from the optoelectronic analgesimeter TF - 003 before and after anesthesia. Intensity of thermal nociceptive exposure has been adjusted so that the initial tail withdrawal response occurred with a latency period in the range 3-6 seconds. First the pain threshold was measured. Then made uniform injection root of the rats tail with four sides with a solution of the test compounds and reference drug in a volume of 1 ml. Control animals the same manner and in the same volume of physiological saline were administered. Irritation deposited on 1 cm distal to the injection site. After the introduction of the test substances and reference preparations tested again with a certain interval of time. Increased latency of the tail flick reflex in 2 times assessed as complete anesthesia. The compounds and reference preparations (procaine, lidocaine, trimecaine) were compared at the time of occurrence of anesthesia, duration of complete anesthesia and the total duration of the anesthetic action of preparation.
Results of the investigations
It was found that among all investigations compounds the substance MAV-184 showed the most activity in the parameter duration of complete anesthesia. Complete anesthesia caused by them was 42.5 minutes.
Compounds MAV-178 and MAV- 185 had moderate activity. MAV-182 showed certain activity, conceding to all compounds. Indicator of duration of complete anesthesia MAV-184 in 1% solution didn't differ that trimecaine.
As can be seen from the data MAV-178 and MAV-185 trimecaine were lower in this series of experiments about 3.5 times.
The 1% solution of MAV-184 was slightly weaker than lidocaine, MAV-178 and MAV-185 concede to him on this parameter approximately 4.6 and 5 times, respectively.
MAV-184 exceeded the parameter of complete anesthesia of novocaine, although this difference was not statistically significant, while the MAV-178 and MAV-185 conceded to him approximately 2.5 and 2.7 times.
Based on the total duration of action, the compounds are grouped into certain manner.
The first group includes MAV-184, the second group includes the MAV-178 and MAV- 185.
As seen from the results in the table №1, MAV-184 in this series provided a pronounced effect, slightly higher than the parameter of total duration of trimecaine. MAV-178 and MAV-185 acted shorter than trimecaine about 2 times.
MAV-184 on parameter of the total duration of action acted weaker than lidocaine. MAV-178 and MAV-185 were inferior to lidocaine in this series of experiments 3 or 4 times.
The 1% solution of MAV-184 in the parameter of total duration of action was higher of novocaine, although this difference was not statistically significant. MAV-178 and MAV-185 is somewhat shorter than him.
16 № 3(3), Vol.2, November 2015
WORLD SCIENCE
Table 1. Activity and duration of action of 1% concentration of the compounds in conduction anesthesia.
Compound, preparation 1 %
The duration of complete anesthesia, min. Duration of action, min.
MAV-178 14,16±3,76 P 2 <0,01 p2 <0,02 p3 >0,05 22,5±3,3 P2 <0,02 p2 < 0,002 P3 >0,05
MAV-184 42,5±4,62 Pi>0,05 p2 >0,05 P3 >0,05 60,0±5,4 P1 >0,05 p2 >0,05 P3 >0,05
MAV-185 13,3±3,2 p1 <0,002 p2 <0,05 P3 <0,02 30,0±3,8 P1 <0,05 p2 <0,01 P3 >0,05
Trimecaine 47,3±8,4 56,9±12,8
Lidocaine 65,0±18,4 90,0±18,4
Novocaine 35,2±7,1 42,3±13,6
Notes: pi- correlation coefficient compared to trimecaine; p2 - compared to lidocaine; p3 -compared to novocaine.
Thus, analysis of experimental data of tested compounds shows that they are effective in varying degrees in conduction anesthesia. MAV-184 is the most active from the all investigated substances, which is interest for the further study.
REFERENCES
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3. Kallio H., Uusitalo R.J., Maunuksela E.L. Topical anesthesia with or without propofol sedation versus retrobulbar /peribulbar anesthesia for cataract extraction: prospective randomized trial. // J.C.R.S. 2001. - V.27, N.10. -P. 1643-1650.
4. Karp C.L., Cox T.A., Wagoner M.D. et al. Intracameral anesthesia: a report by American Academy of ophthalmology.// Ophthalmology 2001.-V.108, N.9.-P. 1704-1710.
5. Kim S., Yang Y., Kim J. Tolerance of patients and postoperative result: topical anesthesia for strabismus surgery. // J. Pediatr. Ophthalmol. Strabismus. 2000. - V.37, N.6. - P.344-348.
6. Осипова Н.М., Новиков Г.А., Петрова В.В. и др. Опиатные и опиоидные анальгетики в лечении острого и хронического болевого синдрома // Синтез, фармакология и клинические аспекты новых обезболивающих средств - Тезисы докладов Всесоюзной конференции - Новгород -1991, с.140
7. Пралиев К.Д., Ю В.К., Фомичева Е.Е. и др. Производные пиперидина: взаимосвязь структуры с обезболивающей активностью // Синтез, фармакология и клинические аспекты новых обезболивающих средств - Тезисы докладов Всесоюзной конференции - Новгород - 1991, с.106
8. Yepez J., Cedeno de Yepez J., Averalo J.F. Topical anesthesia for phacoemulsification, intraocular lens implantation and posterior vitrectomy. // J. Cataract Refract. Surg.-2003. V.26, N.4. -P.475.
9. Шайда Л.П., Лампусова В.Б., Стягайло C.B. Клиническая фармакология средств для обезболивания стоматологических вмешательств // Эндодонтия today. - 2002. - № 3-4. - С. 79-93.
10. Лампусова В.Б., Проблема недостаточной эффективности местного обезболивания в клинике терапевтической стоматологии // Стоматология. - 2006. - Т. 85, № 6. - С.6-10.
II. Стягайло C.B. Оценка эффективности местного инъекционного обезболивания в зависимости от стоматологической патологии и групповой принадлежности зуба // Стоматологический журнал. - 2007. -№2.-С. 61-62.
12. Стягайло C.B. Эффективность местной анестезии современными анестетиками при лечении пульпита и кариеса // Клиническая медицина. Вопросы клиники, диагностики, профилактики и лечения. Том 15. -Великий Новгород - Алматы, 2007. - С. 373-380.
