CC BY
14STUDY SPECIFIC ACTIVITY AMONG OF PYRIDINE DERIVATIVES ON THE MODEL OF CONDUCTION
ANESTHESIA
Raimkulova K. B., Kim 1.1., Pichkhadze G. M.,
students: Tyrsinbekova Zh. Sh., Moldakul Y. M., Maratova Sh. I.
KazNMUnamed by S. D.Asfendiyarov, Almaty, Kazakhstan
Abstract. The problem of eliminating and preventing pain remains the most urgent problem of medicine. Local anesthesia is the most simple and most importantly, safe method of pain relief. The proportion of this type of anesthesia is increased recently [1-4]. This is related with the improvement of representation of the role of local anesthesia, as well as the emergence of new local anesthetics. Currently, a large number ofpreparations for topical analgesic effect of various pharmacological groups are synthesized, which differ in effectiveness of anesthesia and duration of its toxicity. But at the same time, the clinic uses a limited number of drugs that are used in various branches of modern medicine. This is due to the fact that many of them do notfully meet the modern requirements for local anesthetics [5-12].
The purpose of this work. The search for compounds having certain advantages over existing local anesthetics in terms ofduration ofaction, 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-176, MAV-180, MAV-183 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 and discussion.
Analysis of the tested substances in the conduction anesthesia presented in table №1 showed that compound MAV- 183 had the most activity for the duration of complete anesthesia. MAV-176, MAV-180 showed moderate effect in descending order of activity. MAV-182 was the weakest compound.
As can be seen from the results in the table MAV-183 on parameter of full anesthesia slightly exceeded to trimecaine. Compounds with moderate activity (MAV-176, MAV-180) on this parameter yielded trimecaine from 1.9 to 3.1 times, respectively.
It was established that the most active substance under the code MAV-183 was slightly weaker than lidocaine and compounds with moderate activity (MAV-176, MAV-180) acted shorter than lidocaine in 2.6 and 4.3 times respectively.
In comparison with novocaine MAV-183 by duration complete anesthesia was more active last about 1.5 times. The duration of complete anesthesia MAV-176, MAV-180 was slightly inferior to that of novocaine.
Proceeding from the activity of the compounds grouped on the parameter of the duration of action they are conditionally divided into 2 groups.
The first group includes substances that have a lasting effect (MAV-183, MAV-180).
The second group includes those compounds acting shorter (MAV-176).
In total duration of action preparations of first group except the MAV-180 were several active trimecaine and MAV-180 corresponded to it on this indicator.
The compounds of the first group (MAV-180, MAV-183) somewhat inferior on the parameter of duration of action corresponding indicator of lidocaine. In this series of experiments MAV-176 acted weaker than lidocaine in 2 times.
As can be seen from the results of table, MAV-183, MAV-180 on indicator of total duration of action were more active than novocaine. The 1% solutions of MAV-176 for the parameter of total duration of action were not different from novocaine.
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-176 25,0±3,1 7 P1 <0,02 p2 <0,05 p3 >0,05 45,0±1,2 P1 >0,05 p2 <0,02 P3 >0,05
MAV-180 15,0±5,14 P1 <0,01 p2 <0,05 p3 >0,05 55,0±3,1 P1 >0,05 p2 >0,05 P3 >0,05
MAV-183 50,0±1,29 P1 >0,05 p2 >0,05 P3 <0,02 70,0±7,4 P1 >0,05 p2 >0,05 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 may conclude that all investigated substances showed a certain local anesthetic effect in conduction anesthesia. The most effective substance - MAV-183 has advantages over trimecaine and novocaine in the plan of the duration of action and is interested for further study.
REFERENCES
1. Heuermann T., Hartman C., Anders N. Long-term endothelial cell loss after phacoemulsification peribulbar anesthesia versus intracameral lidocaine 1% prospective randomised clinical trial. // J.Cataract Refract. Surg.- 2002. -V.28, N.4. -P.639-643.
14 № 3(3), Vol.2, November 2015
WORLD SCIENCE
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.
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.
