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I Abstracts. PHYTOPHARM 2017
NEUROPROTECTIVE DRUGS OF PEPTIDE STRUCTURE
© Petr D. Shabanov
Military Medical Academy, St.Petersburg, Russia; Institute of Experimental Medicine NWB RAMS, St.Petersburg, Russia
There are several drugs of peptide nature using in the modern medicine as neuroprotective drugs: cerebrolysine and cortexin (both derivatives from the mammals brain), synthetic peptides of low molecular weight noopept, semax, dilept, selank, astessin, deltaran, gene-engineering peptides like antorex, etc [1, 3, 5, 7]. According to the conception of neuroprotection widely spreaded in neurology, neuroprotectors are shown to propose a number of specific requirements [1]: 1) to have nootropic or nootropic-like effects consisting of an ability to improve the resistance of the organism, and the central nervous system in particular, to action of different damaged factors simultaneously with maintenance or enhancement of the higher functions of the brain; 2) to optimize metabolic activity of neural cells in action of aggressive factors of the environment; 3) to recover of impaired metabolism and energy deficit in neural cells; 4) to have anti-oxidative (anti-free radicals) effect; 5) to activate directly neurotrophic processes by means of stimulation of sprouting and formation of neurotrophic factors; 6) to prevent neuronal degeneration due to different pathological processes (autoimmune, toxic, aged, accelerated apoptosis). Among the candidates reviewed for these positions it should be consider cortexin, a peptide organ/tissue drug derived from the porcine brain cortex. The comparative investigation of a number peptide drugs (brain tissue drugs cerebrolysine and cortexin, synthetic peptides semax, selank, deltaran, noopept, dilept) in experimental and clinic conditions showed their high neuroprotective activity. It was registered both after administration of drugs into the brain ventriculi and after systemic (intraperitoneal) administration. The direction of effects after both types of administration was similar that indicated the peptide drugs penetrated the brain blood barrier. Moreover, the peptides were effective in diminution of subsequences following prolong social isolation, activation of the stress/antistress systems in early ontogeny [1], in experimental ischemia of the brain after occlusion of both carotid arteries, in traumatic toxicosis, after mechanic brain injury [7], in elevated seizure activity. In clinic, cortexin, cerebrolysine, semax and noopept were effective in postabstinent period in patients with alcoholism, in heavy somatic patients suffered from asthenic syndrome, in brain damaged patients, in children with seizure syndrome, after intoxication with neurotropic poisons, for acceleration of acclimatization in quick changes of meteorological conditions of environment. It is important to emphasize that brain tissue drugs, cortexin in particular, were clinically more effective than synthetic neuropeptides, though in the experimental conditions their pharmacological activity often was higher than of brain tissue drugs. Besides, all drugs of metabolic type of action possessed an individual sensitivity to treatment when a half of patients reacted on drug brightly, but another one reacted by minimal improvement [2, 4, 6].
The special accent has been done to analyze homeostatic values changes in military men performing training-combat tasks in extreme conditions depending on metabolism regulator genes polymorphism [3, 5]. There was recognized interrelation of different genes alleles TFAM, PPARA and PPARGC1A with successful adaptation to high exercise load at performing training-combat tasks. There was carried out pharmacologic analysis of metaprot, cytoflavin, cortexin and gliatilin effect to functional state of military men at performing training-combat tasks in extreme conditions. Metaprot was shown to effect on adaptation mechanisms positively both at biochemical and organs system level considerably decreasing rehabilitation period. Cytoflavin effected positively on adaptation mechanisms too, basically during the period of rehabilitation. Meanwhile cytoflavin decreased time necessary for rehabilitation for those military men who have different combinations of homozygous alleles (TFAM Ser, PPARA C and PPARGC1A Ser) associated with lower aerobic productivity values. Cortexin effected positively on physiological systems of blood circulation and respiration, increases physiological reserves of the body, more efficient for military men who had different combinations of homozygous alleles (TFAM Ser, PPARA C and PPARGC1A Ser) associated with lower aerobic productivity values; had no effect during rehabilitation period and basal metabolic rate.
Therefore, peptide neuroprotectors should be consider as perspective drugs for the treatment of many diseases of the central nervous system where both neuronal degeneration and reduction of metabolic status of the neural cells are the leading pathophysiological factors.
References:
1. Diakonov MM, Shabanov PD. 2015. Neurologia I neu-rokhirurgiya. East Europe. 226):147-153.
2. Khokhlov PP, Lebedev AA, Bychkov ER, Shabanov PD. 2016. Stress, Brain and Behavior. 5:49-50.
3. Kozlova AS, Pyatibrat AO, Mel'nov SB, Smolnik NS, Shabanov PD. 2015. Obzory po klinicheskoi pharma-cologii I lekarstvennoi terapii. 13(2):43-48.
4. Lebedev AA, Pshenichnaya AG, Bychkov ER, Yakushi-na ND, Shabanov PD. 2016. Obzory po klinicheskoi pharmacologii I lekarstvennoi terapii. 14 (4):24-31.
5. Pyatibrat AO, Mel'nov SB, Kozlova AS, Apchel VY, Pyatibrat ND, Shabanov PD. 2015. Vestnik Voenno-meditsinskoi akademii. 2(50):29-36.
6. Tissen IY, Vinogradov PM, Khokhlov PP, Lebedev AA, Bychkov ER, Shabanov PD. 2015. Eur. Neuro-psychopharmacology. 25 (Suppl 2):S269-S270.
7. Zarubina IV, Buznik GV, Shabanov PD. 2015. Pediatr. 6(3):56-61.
Obzory po kliniceskoj farmacologii i lekarstvennoj terapii [Reviews of clinical pharmacology and drug therapy] vol. 15/2017/suppLement 1
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