Succinates adaptogenic and actoprotective activity: experiences with hydroxymethylethylpyridine succinate (mexidol) in handball



Associate professor, Ph.D. A.Yu. Khrebtova
Associate professor, Ph.D. N.A. Shalamova
Ural State University of Physical Culture, Chelyabinsk


Keywords: skilled handball players, multi-tour system of competitions, overall performance, special endurance, 3-roxy-6-methyl-2-ethylpyridine succinate, actoprotective activity, aerobic glycolysis.

Introduction. One of the current issues of modern elite sport is to find and use non-performance enhancing substances of pharmacological correction aimed at maintaining a proper level of physical performance in the conditions of high competitive activity. Today the multi-tour system of competitions in the Russian Handball Premier League Championship creates conditions in which the preparatory training stage is reduced and the duration of the actual season significantly increases [9]. This characteristic of professional activity of handball players requires more effective realization of adaptive capacity of athletes’ bodies and the presence of a functional ability to keep a stable high fitness level throughout all the key stages of the qualifying tournament of the championship of Russia. Rational use of biologically active substances in the form of medicines and dietary supplements, obligatory compliance of the WADA requirements and limitations, is currently a significant factor in achievement of high sports results. For this reason multifunctional medications that provide a wide range of therapeutic impacts improving energy metabolism in cells are of special interest. From this point of view derivatives of 3-oxypyridine, in particular 3-oxy-6-methyl-2-ethylpyridine succinate (mexidol) are one of the promising means of optimizing the aerobic processes of energy supply of muscle cells, increasing resistance to oxygen dependent pathological processes and body resistance to the impact of intense physical loads.

The purpose of the research is to determine the effectiveness of oxymethylethylpyridine succinate in a complex of measures aimed at increasing the maximum capacity of the aerobic processes of energy supply in order to enhance the overall physical working capacity, aerobic and strength endurance of highly skilled athletes of competitive sports.

Research methods and organization. During a short (2 months long) pre-season period of a men’s professional handball team which plays in the multi-tour system of competitions in the Russian Handball Premier League Championship that is about 8-9 months long [2], a placebo-controlled study of the efficacy of oxymethylethylpyridine succinate was conducted. A synthetic antihypoxant with antioxidant and anxiolytic properties has a wide spectrum of pharmacological actions. It is known that salts and ethers of succinic acid (succinates) increase the body resistance to a wide range of stress factors (hypoxia, ischemia, inflammation, intoxication, lactate acidosis) [10, 12]. In particular, mexidol has been clinically proved effective for treatment of different types of hypoxia. At the same time oxymethylethylpyridine succinate protects body cells from the ischemia and acidosis damage, normalizing metabolism in tissues, it increases aerobic glycolysis and improves oxygen absorption. However, mexidol molecules have a high penetration power against succinic acid and thereby initiate the use of pyridine and succinate residues in the Krebs cycle as energy substrates and thus maintain adenosine triphosphate synthesis under hypoxia at a particular level. Activation of succinate oxygenated oxidation under hypoxia promotes resistance increase of cells of brain, myocardium, liver and skeletal muscles to oxygen deficiency and determines the antihypoxic action mechanism. Nootropic properties of mexidol are manifested in its ability to improve learning and memory, help keep memory trace and resist fading of obtained skills and reflexes, which is especially important in comprhensive coordination and competitive sports. The compound has an original mechanism of action, the fundamental difference of which from the action mechanism of traditional neuropsychotropic products is its lack of specific binding with known receptors that excludes a psychogogic effect and the possibility of addiction. Stress-relieving and anxiolytic effects of the compound are important in elite sport in terms of reducing the risk of development of fatigue and maladaptive exhaustion during multi-tour competitions of high intensity. Acceleration of recovery against the background of the asthenic syndrome after viral infections associated with detoxification by normalizing metabolism and increasing cells’ energy reserves as a result of their direct replenishment is also an important ground for using the compounds by highly skilled athletes.

To achieve the set goal a comprehensive examination of 22 handball players of the Lokomotiv-Polet men’s Super League team from the city of Chelyabinsk was conducted during training camps (TC). Most of the examined athletes (12 persons) were ranked Master of Sports, the second largest in number were Candidate for Masters of Sports (6 persons) and Masters of Sports of International grade (4 persons). Groups were formed based on the age of the subjects. The experimental group (EG) included athletes over 23 years old, the control group (CG) – younger ones. In terms of this indicator the groups differed significantly by 1.3 times (р<0.05). According to the results of the advanced medical examination (AME) the number of diagnosed diseases among the athletes from the experimental group exceeded the reference value by 1.7 times (р<0.05).

Fitness level assessment and evaluation of the compound effectiveness were conducted by three main components: health status, morphological and functional characteristics and parameters of overall and special physical fitness of athletes [4-6]. Functional examination of all athletes was conducted in a gym. There were determined biochemical parameters such as: capillary blood lactate and glucose levels, total creatine phosphokinase activity, severity of enzymemia by the aspartate and alanine transaminase activity criteria.

The research was carried out during three training camps:

  1. Recovery TC (1) was held in Chelyabinsk region, on lake Chebarkul from July 15h, 2006 till July 25th, 2006. Oxymethylethylpyridine succinate (mexidol, manufactured by LLC NPK Pharmasoft) was prescribed for taking in the morning by 250 mg for 8 days in the experimental group (from July 18th till July 25th), and a placebo was prescribed in the similar dose in the control group.

  2. Inducing TC (2) - «middle altitude» - was held in the training center «Yunost’» (Chelyabinsk region, the town of Asha), from July 30th, 2006 till August 13th, 2006. Oxymethylethylpyridine succinate was prescribed for taking in the morning and in the evening by 250 mg in the experimental group, and a placebo was prescribed for taking in the morning and in the evening in the similar dose in the control group.

  3. Pre-season TC (3) a «friendly tournament» was held in a training center (Chelyabinsk region, the town of Satka) from August 16th, 2006 till August 28th, 2006. During the last three days of this period a friendly tournament for the Governor Cup of Chelyabinsk region was held. Oxymethylethylpyridine succinate was not used.

Research results and discussion. In terms of all monitored indicators of the functional state of the athletes no significant differences between groups were detected at the beginning of TC (1). However, after the training camp the HR at rest decreased by 13.4 % (р = 0.022) on average from the initial figure in the experimental group and was significantly lower in comparison with the indicators in the control group (р=0.046). Reduced sympathetic influences of the autonomic nervous system on the cardiovascular system of athletes, signs of “economization” of the central hemodynamics and significant bradycardia against the background of taking mexidol [1, 8] indicate more efficient adaptation of the athletes of the experimental group to physical loads at the end of TC (1). It should be noted that by the end of the training camp the value of the diastolic component of blood pressure decreased from the initial value by 15.6% (p = 0.029) on average in the experimental group, which can be explained by antihypoxic and mild hypotensive effects of the compound [7] and indicates a more adequate response of the bodies of EG athletes to physical loads. It is important to note that no significant changes were detected in either of the groups during TC (1) with regards to all the other monitored functional indicators. According to the results of a 6-minute run (the Cooper test) no significant differences were detected between the groups at the beginning and at the end of the training camp. However, a significant improvement of this indicator by 5.6% (p = 0.046) was recorded within the main group at the end of TC (1). These changes show an increase of the overall aerobic capacity of athletes in the process of training against the background of taking mexidol by optimizing the oxygen utilization mechanisms of the tissues involved and increase of glycogen oxidation in mitochondria [1]. Consequently, there are reasons to assume that oxymethylethylpyridine succinate demonstrates its effectiveness as an adaptogen and an actoprotector under these conditions.

During the rest period between the training camps the athletes of both groups continued to take their preparations by the following scheme: 250 mg twice a day in the morning and in the evening for 18 days from July 26th, 2006 till August 13th, 2013. By the start of TC (2) none of the indicators of the functional state significantly changed compared with those at the end of TC (1), with the exception of the overall probability of maladaptive response that significantly decreased by 1.4 times (р<0.05) in the experimental group, indicating an improvement in the recovery processes during the period of rest between training camps against the background of a double increase of the daily dose of mexidol. None of the analyzed indicators significantly changed by the beginning of TC (2) compared to initial values.

It should be noted that unlike the experimental group, in the control group in the first test of motor skills parameters in a comprehensive exercise which helped assess special endurance of handball players, the average indicator of pre-start HR0 characterizing stress resilience and the level of instability of the neurodynamic component monitoring of the functional state of an athlete demonstrated a significant increase (р<0.05), indicating instability of the central and humoral regulatory mechanisms of the cardiovascular system of younger athletes. By the end of TC (2) an increase of the value of the overall probability of maladaptive response by 1.4 times was recorded with the athletes of the experimental group compared with those of the control group against the background of a statistically significant decrease of the systolic and diastolic components of blood pressure as well as HR.

The intensity of the special work (M) performed by the athletes of the experimental group was significantly lower by 1.3 times (p = 0.046) compared with the control group. It should be noted that the pre-start and maximum HR in the experimental group was also lower than the control values by 1.3 (р<0.05) and 1.2 (р<0.05) times, respectively. The transition from the large (mixed, with a predominantly aerobic mechanism of energy supply) power zone into submaximal (anaerobic and glycolytic) one also occurred at significantly – by 1.3 times (р<0,05) – lower HRм values, indicating a decrease of the aerobic component in the overall contribution of energy production during special work performance of the experimental group players. However, the time spent to perform the comprehensive exercise did not differ in the groups, indicating a higher technical and professional qualification of the experimental group.

Consequently, continuous and long-lasting (over 25 days) intake of oxymethylethylpyridine succinate by highly skilled athletes against the background of adaptation to middle altitude is impractical as it is accompanied by an imbalance of certain functional parameters indicating a redistribution in the energy supply mechanisms towards anaerobic glycolysis and showing a decrease in the power of the anaerobic component and the possibility of utilizing oxygen in the working muscles. Owing to such an adaptive trace occurring in case of long-term intake of the preparation we can talk about a decrease of the values of aerobic and strength endurance of athletes. Some sources describe the changes developing in case of a long-term intake of mexidol, the physiological effect of which is related to maintaining the energy balance in the body and redistributing oxygen consumption in favor of the brain tissue [11]. The results obtained in this research require further study.

At the end of TC (2) intake of the compounds was stopped. By the start of TC (3) and after it the functional state of the athletes in both of the groups was comparable, no significant differences in the monitored indicators were found. However, the time of performing a special comprehensive exercise was significantly better by 8% (р<0.05) in the main group by the end of TC (3) against the background of preceding intake of the studied compound. The criteria of effectiveness of the neurodynamic component of the motor qualities control and energy supply system in the groups did not differ significantly.

The time of performing the comprehensive exercise by older athletes of the experimental group improved by 10% (p = 0.019) by the end of TC (3) compared with the initial values. In the control group the values significantly improved by 3.1% (p = 0.05) only. Thus, it can be concluded that there is a beneficial effect of taking oxymethylethylpyridine succinate in terms of improving motor and functional training of highly skilled handball players.

Conclusion. The carried out study leads to the conclusion about the presence of adaptogenic, stress limiting and actoprotective properties of oxymethylethylpyridine succinate with regards to skilled handball players during the recovery training camp in the dose of 250 mg daily for 8 days. The use of this compound makes it possible to maintain a good level of functional fitness of older athletes. Use of the compound is combined with the improvement of sports result of older athletes while working in the large power zone. In addition, parameters improvement during the submaximal power zone test is registered for these athletes, which indicates a positive delayed effect of the compound. The following effective schemes of using oxymethylethylpyridine succinate can be proposed: as an adaptogen to the conditions of middle altitude - 2-4 capsules (250-500 mg) in the morning and in the evening before meals for 8-10 days, starting 10 days before the start of the training camp; as an actoprotector during intensive physical work in the conditions of hypoxia - a dose of 250 mg (2 times a day, in the morning and in the evening before meals) for not more than 5-7 days, but only in the case of synergistic use with groups of metabolic preparations. In particular, medications and dietary supplements containing substrates of tricarboxylic acids cycle (malic acid and its derivatives, α-ketoglutaric and fumaric acids). As an antioxidant and an antihypoxic preparation for recovery - the dose of 500 mg (twice a day in the morning and in the evening before meals) for 2-3 weeks along with aerobic exercise of low and medium intensity. One should stop taking the preparation 7-10 days before the start of competitive activities.


  1. Avakyan, O.M. Farmakologicheskaya regulyatsiya funktsiy adrenoretseptorov (Pharmacological regulation of adrenoceptor functions) / O.M. Avakyan. – Moscow: Meditsina, 1988. – 256 P.
  2. Alyoshin, I.N. Model' godichnogo tsikla podgotovki gandbolistov vysokoy kvalifikatsii: avtoref. dis. kand. ped. nauk (Model of annual training cycle for highly skilled handball players: abstract of Ph.D. thesis) / I.N. Alyoshin. – Chelyabinsk, 2004. – 23 P.
  3. Astrand, P.O. Faktory, obuslavlivayushchie vynoslivost' sportsmenov (Factors causing endurance of athletes) / P.O. Astrand // Nauka v Olimpyyskom sporte. – Kiev, 1994. – P. 43–47
  4. Baryshev, G I. Podgotovka gandbolistov v predsorevnovatel'nom etape s uchyotom dannykh tekushchego kontrolya: avtoref. dis. ... kand. ped. nauk (Training of handball players in pre-season in view of monitoring data: abstract of Ph.D. thesis) / G.I. Baryshev. – Malakhovka, 1981. – 20 P.
  5. Evgen'eva, L.Ya. Dinamika funktsional'nykh pokazateley organizma gandbolistov na zaklyuchitel'nom etape podgotovki k otvetstvennym sorevnovaniyam (The dynamics of functional parameters of the body of handball players at the final phase of training for major competitions) / L.Ya. Evgen'eva // Morfofunkcional'nye, fiziologicheskie i biokhimicheskie osnovy sovershenstvovaniya trenirovochnogo protsessa. – Kiev: KGIFK, 1980. – P. 58-67
  6. Ignat'eva, V.Ya. Gandbol: uchebnik dlya IFK (Handball: textbook for institutes of phys. cult.) / V.Ya. Ignat'eva. – Moscow: Fizicheskaya kul'tura, 2008. – 375 P.
  7. Konovalova, E.A. Korrektsiya endotelial'noy disfunktsii kombinatsiey L-norvalina i meksidola (Correction of endothelial dysfunction using L-norvaline and mexidol together) / E.A. Konovalova, E.S. Chernomortseva, M.V. Korokin, T.G. Pokrovskiy, E.N. Dudina // Nauchnye vedomosti BGU: meditsina, farmatsiya. – Belgorod, 2012. – № 4, Iss. 17/1. – P. 175–182.
  8. Meerson, F.Z. Adaptatsiya k stressornym situatsiyam i fizicheskim nagruzkam (Adaptation to stress situations and physical load) / F.Z. Meerson, M.G. Pshennikova. – Moscow: Meditsina, 1988. – 256 P.
  9. Mikhalev, V.I. Osobennosti struktury trenirovochnogo protsessa muzhskikh gandbol'nykh komand vysshey ligi v sorevnovatel'nom periode (Structural features of training process of male handball premier league teams in actual season) / V.I. Mikhalev, O.S. Shalaev, N.P. Filatova, O.N. Kudrya, A.Yu. Aseeva // Teoriya i praktika fizicheskoy kul'tury. – 2014. – № 12. – P. 71–77.
  10. Mikhin, V.P. Primenenie meksidola v terapii ostrogo koronarnogo sindroma (Mexidole for treatment of acute coronary syndrome) / V.P. Mikhin, L.D. Smirnov, N.V. Vasil'eva // Mater. 8-go Kongressa «Chelovek i lekarstvo» (Proceedings of the 8th Congress "Man and medicine"). – Moscow, 2001. – P. 189–194.
  11. Tiganov, A.S. Klinicheskie ispytaniya meksidola v kachestve trankvilizatora s nootropnym komponentom deystviya (Clinical trials of mexidol as tranquilizer with nootropic agent) / A.S. Tiganov, V.A. Kontsevoy, A.B. Smulevich // Nauchny tsentr psikhicheskogo zdorov'ya RAMN. – Moscow, 2002. – 64 P.
  12. Fedin, A.I. Neyroprotektor s antioksidantnymi i antigipoksantnymi svoystvami meksidol v terapii ishemicheskogo insul'ta (Neuroprotective drug mexidol having antioxidant and antihypoxic properties in treatment of ischemic stroke) / A.I. Fedin, S.A. Rumyantseva, V.N. Evseev. – Moscow: Meditsina, 2006. – 21 P.

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