Antiarrhythmic and proarrhythmic action of uridine and uridine nucleotides. Cognitive process and cognition

Compound

1 vial with lyophilized powder contains cytidine-5-monophosphate disodium salt 10 mg, uridine-5-triphosphate trisodium salt, uridine-5-diphosphate disodium salt, uridine-5-monophosphate disodium salt only 6 mg (corresponding to 2.660 mg of pure uridine).
Excipients: mannitol; solvent: water, Na chloride.

pharmachologic effect

Indications for use

Mode of application

Nucleo c.m.f. forte ampoules for intramuscular administration
Before administration, it is necessary to dissolve the powder with the supplied solvent. Adults, as well as the elderly and children under 14 years of age, are prescribed 1 injection 1 time per 24 hours. Children from 2 to 14 years of age are prescribed 1 injection every 48 hours.
The course of treatment is from three to six days, then oral administration of the drug is continued from 1 to 2 capsules twice a day for 10 days. If there are indications, the drug can be extended up to 20 days.

Side effects

Contraindications

Pregnancy

Overdose

Release form

Storage conditions

Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide on the appointment of the drug, as well as determine the dose and methods of its use.

4.2.1. Primary structure of nucleic acids called sequence of mononucleotides in a DNA or RNA chain . The primary structure of nucleic acids is stabilized by 3",5"-phosphodiester bonds. These bonds are formed by the interaction of the hydroxyl group in the 3 "-position of the pentose residue of each nucleotide with the phosphate group of the adjacent nucleotide (Figure 3.2),

Thus, at one end of the polynucleotide chain there is a free 5'-phosphate group (5'-end), and at the other end there is a free hydroxyl group in the 3'-position (3'-end). Nucleotide sequences are usually written in the direction from the 5" end to the 3" end.

Figure 4.2. The structure of a dinucleotide, which includes adenosine-5"-monophosphate and cytidine-5"-monophosphate.

4.2.2. DNA (deoxyribonucleic acid) is contained in the cell nucleus and has a molecular weight of about 1011 Da. Its nucleotides contain nitrogenous bases. adenine, guanine, cytosine, thymine , carbohydrate deoxyribose and phosphoric acid residues. The content of nitrogenous bases in a DNA molecule is determined by the Chargaff rules:

1) the number of purine bases is equal to the number of pyrimidine ones (A + G = C + T);

2) the amount of adenine and cytosine is equal to the amount of thymine and guanine, respectively (A = T; C = G);

3) DNA isolated from cells of different biological species differ from each other in the value of the specificity coefficient:

(G + C) / (A + T)

These patterns in the structure of DNA are explained by the following features of its secondary structure:

1) a DNA molecule is built from two polynucleotide chains linked by hydrogen bonds and oriented antiparallel (that is, the 3 "end of one chain is located opposite the 5" end of the other chain and vice versa);

2) hydrogen bonds are formed between complementary pairs of nitrogenous bases. Adenine is complementary to thymine; this pair is stabilized by two hydrogen bonds. Guanine is complementary to cytosine; this pair is stabilized by three hydrogen bonds (see figure b). The more G-C pairs in a DNA molecule, the greater its resistance to high temperatures and ionizing radiation;

Figure 3.3. Hydrogen bonds between complementary nitrogenous bases.

3) both DNA strands are twisted into a helix having a common axis. Nitrogenous bases face the inside of the helix; in addition to hydrogen interactions, hydrophobic interactions also arise between them. The ribose phosphate parts are located along the periphery, forming the backbone of the helix (see Figure 3.4).

Figure 3.4. Diagram of the structure of DNA.

4.2.3. RNA (ribonucleic acid) is contained mainly in the cytoplasm of the cell and has a molecular weight in the range of 104 - 106 Da. Its nucleotides contain nitrogenous bases. adenine, guanine, cytosine, uracil , carbohydrate ribose and phosphoric acid residues. Unlike DNA, RNA molecules are built from a single polynucleotide chain, which may contain sections complementary to each other (Figure 3.5). These sections can interact with each other, forming double helixes, alternating with non-spiralized sections.

Figure 3.5. Scheme of the structure of transfer RNA.

According to the features of the structure and function, three main types of RNA are distinguished:

1) messenger (messenger) RNA (mRNA) transmit information about the structure of the protein from the cell nucleus to the ribosomes;

2) transfer RNA (tRNA) carry out the transport of amino acids to the site of protein synthesis;

3) ribosomal RNA (rRNA) are part of ribosomes, participate in protein synthesis.

AMP, GMP and IMP inhibit key reactions of their synthesis. Two enzymes: FRDF-synthetase and amidophosphoribosyltransferase are inhibited only with a simultaneous increase in the concentration of AMP and GMP, while the activity of adenylosuccinate synthetase and IMP-dehydrogenase decreases only with an increase in the amount of the end product formed in each of the branches of the metabolic pathway. AMP inhibits the conversion of IMP to adenylosuccinate, and GMP inhibits the conversion of IMP to xanthosine-5"-monophosphate (CMP), thus ensuring a balanced content of adenyl and guanyl nucleotides.

"Spare" pathways for the synthesis of purine nucleotides play a significant role during periods of active tissue growth, when the main synthesis pathway from simple precursors is not able to fully provide nucleic acids with substrates (Fig. 10.31). This increases the activity

hypoxanthine-guanine phosphoribosyltransferase(GGPRT), which catalyzes the conversion of nitrogenous bases: hypoxanthine and guanine into nitrogen

cleotides - IMP and GMF using FRDF as a phosphoribose donor;

adenine phosphoribosyltransferase (APRT), which synthesizes AMP from adenine and FRDP;

adenosine kinase (AKase), which converts adenosine to AMP by transferringγ-phosphate residue of ATP on the 5 "-hydroxyl group of ribose nu-

cleoside.

Catabolism of purine nucleotides. Hyperuricemia and gout

In humans, catabolism of purine nucleotides ends with the formation uric acid. Initially, nucleotides hydrolytically lose a phosphate residue in reactions catalyzed by phosphatases or nucleotidases. Adenosine is deaminated adenosine deaminase with the formation of inosine. Purine nucleoside phosphorylase cleaves nucleosides to free bases and ribose-1-phosphate. Then xanthine oxidase- aerobic oxidoreductase, the prosthetic group of which includes iron ions (Fe3+), molybdenum and FAD, converts nitrogenous bases into uric acid. The enzyme is found in significant amounts in the liver and intestines and oxidizes purines with molecular oxygen (Fig. 10.32). Uric acid is eliminated from the human body mainly in the urine and a little in the faeces. It is a weak acid and is found in biological fluids in an undissociated form in a complex with proteins or in the form of a monosodium salt - urate. Normally, in the blood serum, its concentration is 0.15-0.47 mmol / l or 3-7 mg / dl. Every day from 0.4 to 0.6 g of uric acid and urates are excreted from the body.

A frequent disorder of purine catabolism is hyperuricemia, which occurs when the concentration of uric acid in the blood plasma exceeds the norm. Due to the poor solubility of this substance against the background of hyperuricemia, gout develops - a disease in which uric acid and urate crystals are deposited in articular cartilage, ligaments and soft tissues with the formation of gouty nodes or tophi, causing inflammation of the joints and nephropathy. Gout affects from 0.3 to 1.7% of the world's population. Men have twice the serum urate pool of women, so they are 20 times more likely to develop gout than women. The disease is genetically determined and is caused by:

– defects in FRDF synthetase associated with hyperactivation or resistance of the enzyme to inhibition by the end products of synthesis;

– partial loss of activity of hypoxanthine-guanine phosphoribosyltransferase, which ensures the reuse of purines.

With a complete loss of hypoxanthine-guanine phosphoribosyltransferase activity, a severe form of hyperuricemia develops - the syndrome

Rice. 10.32. Purine nucleotide catabolism:

1 - nucleotidase or phosphatase; 2 - adenosine deaminase;

3 - purine nucleoside phosphorylase; 4 - guanase; 5 - xanthine oxidase

Lesha-Nykhana, in which neurological and mental abnormalities are observed. The disease is inherited as an X-linked recessive trait and occurs only in boys.

Gout is treated with allopurinol, a structural analogue of hypoxanthine. Xanthine oxidase oxidizes the drug into oxypurinol, which binds strongly to the active site of the enzyme and stops purine catabolism at the stage of hypoxanthine, which is 10 times more soluble in body fluids than uric acid.

Biosynthesis and catabolism of pyrimidine nucleotides. Orotaciduria

In contrast to the synthesis of purine nucleotides, in which the nitrogenous base is formed on a ribose-5-phosphate residue, the pyrimidine ring is initially assembled from simple precursors: glutamine, aspartate, and CO2. Then it interacts with FRDP and turns into uridine-5 "- monophosphate - UMP (Fig. 10.33).

4 Orotat

Dihydroorotate

Amide group

N 1 6 5

2 3 4

Rice. 10.33. Origin of pyrimidine ring atoms and synthesis of UMF:

I - CAD-enzyme: 1 - carbamoyl phosphate synthetase P; 2 - aspartate transcarbamoylase; 3 - dihydroorotase; 4 - Dihydroorotate dehydrogenase;

II - UMP synthase: 5 - orotate phosphoribosyltransferase, 6 - OMP decarboxylase

UMP synthesis proceeds in the cytosol of cells and includes 6 stages catalyzed by 3 enzymes, two of which are polyfunctional. At the first stage, carbamoyl phosphate is synthesized from Gln and CO2 using 2 ATP molecules. When Asp is attached to carbamoyl phosphate and H2O is cleaved, a cyclic compound is formed - dihydroorotate, which is the product of the first polyfunctional protein - CAD-enzyme. The name of the CAD is made up of the initial letters of the enzymatic activities that individual catalytic domains have:

carbamoyl phosphate synthetase P (CPS P), aspartate transcarbamoylase and dihydroorotase . Dihydroorotate is further oxidized to orotate by NAD-dependent dihydroorotate dehydrogenase and with the participation of the second bifunctional enzyme - UMP synthase turns into UMF.

UMP forms UTP in two steps:

the first step is catalyzed by UMP kinase, UMP + ATP → UDP + ADP,

and the second - NDP-kinase with a wide substrate specificity UDP + ATP → UTP + ADP,

CTP is formed from UTP by the action of CTP, a synthetase, which, using the energy of ATP, replaces the keto group of uracil with the amide group Gln:

UTP + Gln + ATP → CTP + Glu + ADP + H3 PO4.

The regulation of the synthesis of pyrimidine nucleotides is carried out allosterically by the negative feedback mechanism:

– UTP inhibits the activity of CPS P in the composition CAD enzyme;

– UMF and CMP inhibit the activity of the second polyfunctional enzyme - UMP synthase;

– accumulation of CTP reduces the activity of CTP synthetase.

Spare pathways in the synthesis of pyrimidine nucleotides do not play such a significant role that in the synthesis of purine nucleotides, although the following are found in cells:

pyrimidine phosphoribosyltransferase, catalyzing the reaction: Pyrimidine + FRDP → Pyrimidine monophosphate + H 4 R 2 O 7 (U or C) (UMF or CMF), uridine kinase, converting nucleoside to nucleotide

Uridine + ATP → UMF + ADP, and uridine phosphorylase, capable of reversing the nucleoside degradation reaction:

uracil + ribose-1-phosphate → uridine + H3PO4.

In the process of catabolism, cytidyl nucleotides hydrolytically lose their amino group and turn into UMF. When inorganic phosphate is cleaved from UMP and dTMP with the help of nucleotidase or phosphatase and ribose with the participation of phosphorylases, nitrogenous bases remain - uracil and thymine. Both heterocycles can undergo hydrogenation with the participation of NADPH-dependent dihydropyrimidine dehydrogenase and hydrolytic cleavage to form β-ureidopropionic from dihydrouracil and β-ureidopropionic from dihydrothymium.

on - β-ureidobutyric acids. Further hydrolytic cleavage of ureido derivatives ends with the formation of CO2, NH4 and β-alanine or β-aminobutyric acid.

Among the metabolic disorders of pyrimidine nucleotides, only one rare hereditary disease has been described - orotaciduria, which occurs as a result of a mutation in the gene of the second polyfunctional enzyme - UMP synthase. In this case, the conversion of orotate to UMF is disrupted, large amounts of orotate (up to 1.5 g per day) are excreted in the urine. Deficiency of pyrimidine nucleotides develops. For the treatment of this disease, uridine or cytidine is used in doses of 0.5 to 1 g per day, which are converted to UMP or CMP by nucleoside kinase, bypassing the impaired reaction.

Formation of deoxyribonucleotides

Usually, the intracellular concentration of deoxyribonucleotides is very low, but in the S-phase of the cell cycle it increases, providing DNA synthesis with substrates. Two enzyme complexes are involved in the formation of deoxyribonucleotides: ribonucleotide reductase and thymidylate synthase.

The reduction of all ribonucleotides to deoxy derivatives is catalyzed by the ribonucleotide reductase complex, which includes the ribonucleotide reductase, restorative protein - thioredoxin and enzyme - thioredoxin reductase, involved in the regeneration of thioredoxin with the help of NADPH (Fig. 10.34).

Ribonucleotide reductase is an allosteric enzyme whose activity depends on the concentration of individual dNTPs, and dATP is an inhibitor of the reduction of all ribonucleotides. This circumstance explains the occurrence of the most severe forms immunodeficiencies with a decrease in the activity of purine catabolism enzymes: adenosine deaminase or purine nucleoside phosphorylase(Fig. 10.32). Deficiency of these enzymes leads to the accumulation of dATP and dGTP in B- and T-lymphocytes, which allosterically inhibit ribonucleotide reductase and deprive DNA precursors. DNA synthesis decreases and cells stop dividing.

The synthesis of thymidyl nucleotides is catalyzed by the thymidylate synthase complex, which includes thymidylate synthase, catalyzing the incorporation of a one-carbon radical into the DUMP molecule, dihydrofolate reductase, providing the restoration of H2-folate to H4-folate with the participation of NADPH, and serineoxymethyltransferase, carrying out the transfer of the hydroxymethyl group Ser to H4 -folate with the formation of N5 N10 -methylene-H4 -folate (Fig. 10.35). In humans, dUMP is formed from dCDP by dephosphorylation followed by hydrolytic deamination.

Among the "spare" ways of synthesis, the following are of particular importance:

thymine phosphorylase, which converts thymine to thymidine: Thymine + Deoxyribose-1-phosphate → Thymidine + H3 PO4 and

thymidine kinase catalyzes the phosphorylation of thymidine. Thymidine + ATP → dTMP + ADP.

Thioredoxin

reductase

Rice. 10.34. Recovery of ribonucleoside diphosphates to deoxy derivatives.

The reducer of ribonucleotides in the form of NDF is thioredoxin, whose sulfhydryl groups are oxidized during this reaction. Oxidized thioredoxin is reduced by thioredoxin reductase with the participation of NADPH

N 5, N 10 - methylene-H 2 - folate

H4 - folate

Serin-

hydroxymethyltransferase

NADPH + H+

Rice. 10.35. Synthesis of thymidine-5"-monophosphate.

Thymidylate synthase not only transfers the methylene group N5 N10 - methylene-H4 -folate to the 5th position of the pyrimidine base of dUMP, but also reduces it to a methyl radical, taking two hydrogen atoms from H4 -folate, therefore replenishing the stocks of N5 N10 -methylene H4 -folate requires the work of two more enzymes: dihydrofolate reductase and serineoxymethyltransferase

Use of nucleotide synthesis inhibitors as antiviral and anticancer drugs

Analogues of nitrogenous bases, nucleosides and nucleotides are widely used in medical practice as drugs (Table 10.3). They can:

– inhibit certain enzymes involved in the synthesis of nucleotides or nucleic acids;

– be included in growing RNA or DNA chains and stop the growth of chains.

Table 10.3

Some anticancer and antiviral drugs

Keltikan is a biologically active food supplement that allows you to restore damage to nerve fibers caused by diseases of the spine and peripheral nervous system. The drug is used in the treatment of neuropathy of various origins.

Release form, composition

Keltikan is available in the form of gelatin capsules for oral administration. The active components of dietary supplements are:

• uridine;
• cytidine-5-monophosphate disodium salt.

Citric acid, magnesium stearate, sodium citrate, mannitol are used as excipients.

pharmachologic effect

The pharmacological action of the drug Keltikan is due to its two-component composition.

• due to uridinimphosphate, there is an acceleration of the process of recovery of damaged nerves;
• thanks to vitamin B12 and folic acid, it is possible to normalize the metabolic processes of neurons - these components support neuronal metabolism, their action is aimed at prevention, as well as reducing the severity of microangiopathy.

The active substances of dietary supplements are able to provide the human body with substances that take part in the formation of the nerve and myelin sheath, and also contribute to better maturation and restoration of nerve fibers, ensuring a stable trophic effect. This allows you to reduce the severity of the inflammatory process, normalize the sensitivity of the affected areas of the nervous system.

Indications

BAA Keltikan is used during treatment:

• osteoarticular neuropathy (sciatica, sciatica);
• metabolic neuropathy (diabetic, alcoholic, polyneuropathy);
• infectious neuropathy;
• inflammation of the trigeminal and facial nerve;
• intercostal neuralgia;
• lumbodynia.

Contraindications

BAA Keltikan should not be used in case of individual intolerance to active or excipients, during pregnancy and breastfeeding. Before using the drug, you should consult with your doctor.

Mode of application

The Keltikan capsule is recommended to be used during the main meal. The exact dosage and duration of use of the drug is determined by the doctor, taking into account the indications for admission and the individual characteristics of the patient's body. If necessary, the course of treatment can be repeated.

If the patient has difficulty swallowing the whole Keltikan capsule, its contents can be removed and drunk separately, without the gelatin shell. It is not recommended to exceed the dosage recommended by the doctor.

The composition of the drug Keltikan does not include lactose and gluten, as well as preservatives and substances of animal origin.

The drug is not a drug. Patients with dysfunction of the urinary or digestive system must necessarily use the drug during the main meal.

Drug interactions with other drugs have not been established. If necessary, dietary supplements can be used with other groups of drugs as prescribed by a doctor.

The drug has a low toxicity, so the likelihood of an overdose is minimal. With the development of any adverse reactions, you should consult a doctor for the appointment of symptomatic treatment.

Patients with a history of diabetes can also use this drug.

During the production of Keltikan capsules, cellulose is used, but this substance is not of animal origin, so vegetarians can use the drug.

The drug does not affect the reaction rate when driving vehicles and performing potentially hazardous activities.

Analogues, cost

The cost of the dietary supplement Keltikan complex for the period March 2017 was formed as follows:

• Capsules for internal use, 20 pcs. - 840-940 rubles.

Keltikan has no exact structural analogues. If it is necessary to select a replacement, it is recommended to consult with your doctor.

Reviews

“The human body consists of a large number of nerve fibers that form the peripheral nervous system. Their defeat (squeezing, infringement, dysfunction caused by chronic diseases) leads to the development of unpleasant, painful sensations: neuralgia. The reserve capabilities of the human body allow you to independently restore the affected fibers, but this process takes a long time. As part of dietary supplement Keltikan there are biogenic components, as well as B vitamins, the action of which is aimed at stimulating one's own recovery processes.

Igor Yurievich, neurologist

“After one course of taking Keltikan, the impressions are ambiguous: I used the drug as an independent remedy, no other drugs were prescribed. I was worried about severe back pain, especially in the morning, after waking up. After various ointments and tablets stopped helping, I found reviews on this dietary supplement on the net. Some write that you need to drink 2-3 packs to have an effect.

Alexander

“Keltikan complex was prescribed by the attending neurologist after two operations to remove a hernia in the lumbar spine. For the second time during the operation, titanium implants were installed, after a repeated recurrence of the disease.

Still worried about the feeling of pain in the back and drugs, whose action is aimed at reducing neuropathy, are always relevant. Preference is given to those drugs that are well tolerated and do not cause addiction and side effects. So, dietary supplement Keltikan had to be ordered through an online pharmacy: the funds were not freely available. The capsule is transparent, through it you can see the contents - small granules. The manufacturer indicates that the granules, if necessary, can be taken without a capsule shell. I took the drug for 20 days - the entire course of treatment. A slight analgesic effect can be noted. For a more pronounced result, it is probably worth using the product longer. ”

Victoria

“I take Keltikan twice a year for prevention purposes. A year ago, there was intense pain caused by a viral infection. She underwent a course of analgesic and antiviral therapy, blockade with Novocaine and Lidaza. Now I support the nervous system with various vitamins and supplements. You need to be prepared for the fact that such a remedy is difficult to find on free sale: I order through a trusted online pharmacy that sells only high-quality and original drugs.

I can recommend such a dietary supplement as an additional source of vitamins and substances that restore nerve fibers. A good remedy for reasonable money (when compared with expensive courses of treatment for neuropathy of an infectious origin). ”

“When the peripheral nervous system is affected, the need for uridine monophosphate increases. Due to its entry into the body from external sources (for example, from dietary supplement Keltikan), regeneration and the process of nerve restoration are accelerated. The drug is used in the complex treatment of neuropathies, it is highly effective and well tolerated. The drug is a quality product, the active substances of which restore damaged nerve tissue. Patients feel better, their physical performance and mental stability increase many times.”

Evgenia Nikolaevna, neurologist

« After the injury, he drank and pierced a large number of drugs, including B vitamins. The Keltikan complex was advised by a doctor friend as an alternative to the more budgetary Neuromultivit. At first, the cost of Keltikan stopped, but after calculating the cost of a course of treatment with one and the other drug, it was decided to try the recommended remedy. The drug turned out to be a dietary supplement, not a medicine - this was the first disappointment. However, after the first course of administration (20 days), I can notice an improvement: the pain has decreased, the reaction to stressful situations has become calmer. This is probably how B vitamins and uridine monophosphate act. I plan to continue the course after the break.”

“I encountered Keltikan on the recommendation of a neurologist from a serious illness of the central nervous system. Having learned that this dietary supplement did not attach any importance and did not buy the drug right away. A few months later, there was a need for an anesthetic, I remembered the recommended dietary supplement. I studied the information: it turned out, what you need. The tool is used to restore the myelin sheath. I drank a course of capsules, there were no side effects. After stopping the drug, it seems that the condition has worsened, so I will continue to take it. ”

“The reception of Keltikan was recommended by a neurologist during exacerbation of neuralgia. This is a German-made dietary supplement, which was used as part of a complex treatment. It is not possible to evaluate this remedy separately, however, in combination with other drugs, there is a positive result. The intense pain has gone, and the remaining ones are gradually disappearing. During the use of adverse reactions did not occur, the drug is easy to take.

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The problem of polypharmacy in the treatment of exacerbation of chronic nonspecific pain in the lower back actualizes the study of innovative drugs that meet the high requirements for an optimal ratio of efficacy and safety. These drugs include nucleotides.
Purpose of the study: to evaluate the efficacy and safety of using Keltikan ® complex in exacerbation of chronic nonspecific pain in the lower back.
Material and methods: The patients were divided into two groups: the 1st group included 20 patients (10 women and 10 men, mean age 44.6±0.84 years) suffering from exacerbation of chronic nonspecific pain in the lower back, who received a set of procedures together with the appointment of the drug Keltikan ® complex (1 capsule 1 time / day with meals) for 20 days; Group 2 included 30 patients (15 women and 15 men, mean age 46.5±1.34 years) suffering from exacerbation of chronic nonspecific pain in the lower back, who received a set of procedures. The effectiveness of therapy was assessed by clinical and psychometric research methods after 20 days of treatment and after 90 days of observation.
results: the study revealed a significant decrease in the intensity of pain in the treatment group with Keltikan ® complex in comparison with the control group after 20 days of therapy and 90 days of observation. When assessing the safety in the group of patients taking Keltikan ® complex with exacerbation of chronic nonspecific pain in the lower back, there were no cases of adverse drug reactions, indicating the safety of the drug.
Conclusion: while taking the drug Keltikan ® complex significantly reduces the severity of pain and improves the quality of life, which allows us to recommend Keltikan ® complex as an adjuvant therapy for this category of patients.

Keywords: nucleotides, Keltikan ® complex, chronic back pain, adjuvant therapy.

For citation: Rachin A.P., Sharov M.N., Vygovskaya S.N., Nuvakhova M.B., Voropaev A.A., Tarasova L.Yu. Experience in the use of a complex preparation of uridine monophosphate in exacerbation of chronic nonspecific pain in the lower back // BC. 2017. No. 24. S. 1812-1817

Experience in the use of a complex uridinemonophosphate drug in the exacerbation of chronic nonspecific lower back pain
Rachin A.P. 1 , Sharov M.N. 2, Vygovskaya S.N. 1 , Nuvakhova M.B. 1 , Voropaev A.A. 1 , Tarasova L.Yu. one

1 National Medical Research Center of Rehabilitation and Balneology, Moscow
2 Moscow State Medical and Dental University named after A.I. Evdokimov

In the conditions of polypragmasy of exacerbation of the chronic nonspecific lower back pain, the problem of research of innovative medications meeting the high requirements of the optimal efficacy and safety ratio, including the nucleotide therapy preparations, is becoming more relevant.
The aim of the study was to assess the efficacy and safety of the use of the Keltikan ® complex in exacerbation of chronic nonspecific lower back pain.
Patients and Methods: patients were divided into two groups: 1 group - 20 patients (10 women and 10 men, mean age 44.6 ± 0.84 years) suffering from exacerbation of chronic nonspecific lower back pain received a complex of procedures together with the appointment of the Keltican ® complex ( 1 capsule 1 time / day during meals) for 20 days. Group 2 composed of 30 patients (15 women and 15 men, mean age 46.5 ± 1.34 years) suffering from exacerbation of chronic nonspecific lower back pain, receiving a complex of procedures. The effectiveness of therapy was assessed by clinical and psychometric methods of the study after 20 days of treatment and after 90 days of observation.
results: the study of pain intensity in the compared groups revealed a significant decrease in this parameter in the "Keltikan ® complex" group in comparison with the "Control" group after 20 days of therapy and after 90 days of observation. In an exacerbation of chronic nonspecific lower back pain, there were no adverse drug reactions in the group of patients taking the Keltikan ® complex, that proves its safety.
Conclusion: the use of the Keltikan ® complex significantly reduces the pain syndrome and improves the quality of life, which makes it possible to recommend the Keltican ® complex as an adjuvant therapy for this category of patients.

key words: nucleotides, Keltikan ® complex, chronic back pain, adjuvant therapy.
For quote: Rachin A.P., Sharov M.N., Vygovskaya S.N. et al. Experience in the use of a complex uridinemonophosphate drug in the exacerbation of chronic nonspecific lower back pain // RMJ. 2017. No. 24. P. 1812–1817.

The article presents the results of a study on the use of a complex preparation of uridine monophosphate (Keltikan complex) for exacerbation of chronic nonspecific pain in the lower back. It has been shown that while taking the drug, the severity of the pain syndrome is significantly reduced and the quality of life is improved, which makes it possible to recommend the Keltikan complex as an adjuvant therapy.

Chronic pain syndrome is an important topical interdisciplinary problem. The medical and social significance of this condition is determined by the high prevalence of headache and back pain among the population, the increase in prevalence with age, and the presence of comorbid disorders, including insomnia and anxiety-depressive disorders.
Over the past decades, a large number of drugs have appeared on the pharmaceutical market for non-specific, often recurrent back pain. At the same time, non-steroidal anti-inflammatory drugs remain the traditionally used drugs for dorsalgia. At the same time, about 40% of patients with back pain do not receive adequate pain relief, suffer from polypharmacy and a high incidence of adverse drug reactions, which makes such treatment unjustified. In such a situation, the relevance of research into innovative drugs that meet the high requirements for an optimal ratio of efficacy and safety, which should include nucleotide therapy drugs, increases.
Nucleotides are low-molecular structural elements that play a fundamental role in metabolic processes, are involved in the conservation of energy and the transfer of certain groups of molecules, and also act as intracellular signaling proteins. In addition, nucleotides are essential components of nucleic acids, in particular DNA and RNA.
Nucleotide uridine monophosphate plays a major role in the neuronal synthesis of all the necessary pyrimidine nucleotides. Penetrating through the membrane into the neuron, the nucleotide quickly turns into di- and triphosphate nucleotides, which have a more pronounced metabolic effect on the repair of nervous tissue. Thus, through biochemical processes, uridine monophosphate that enters the body from outside is metabolized to further nucleotides, which are also included in metabolism and reparative processes.
Uridine monophosphate (50 mg) is the main component of the Keltikan ® complex. In addition to the nucleotide, the Keltikan ® complex also includes vitamin B12 (3 µg) and folic acid (400 µg).
Vitamin B12 is an essential coenzyme for various metabolic reactions. Cyanocobalamin is involved in the synthesis of purine and pyrimidine nucleic bases, nucleic acids and proteins.
Folic acid acts as a coenzyme in many catalytic reactions, especially in the metabolism of protein and nucleic acids, in particular in the synthesis of purine, DNA and the assembly of various amino acids, is involved in the biosynthesis of neurotransmitters, phospholipids and hemoglobin. Thus, Keltikan ® complex is an external source of elements necessary for the repair of nervous tissue.
Keltikan ® complex promotes nerve regeneration, filling the increased need of the nervous tissue for the synthesis or utilization of lipids and proteins. The uridine monophosphate contained in it activates the processes of transcription and translation in the cells of the nervous tissue (synthesis of DNA and RNA). As a result, cell division, metabolism and regeneration of peripheral nerves are stimulated. In addition, uridine monophosphate plays a key role in the process of activation of intra- and extracellular signals that control the complex process of migration/adhesion of Schwann cells to the axon.
The purpose of this study: to evaluate the efficacy and safety of using Keltikan ® complex in exacerbation of chronic nonspecific pain in the lower back.

Material and methods

Research results

On the significant effectiveness of the drug Keltikan ® complex in reducing the intensity of pain in patients suffering from exacerbation of chronic non-specific pain in the lower back, in comparison with the control group receiving a set of procedures.
Our study showed that in patients suffering from exacerbation of chronic nonspecific pain in the lower back, and in the 1st and 2nd compared groups, there were no significant differences before the start of treatment. according to the subjective assessment of pain, the analysis of which was carried out on a verbal scale, and the indicator was 2.5±0.15 and 2.5±0.19 points, respectively.
In the 1st group of patients (Keltikan ® complex, n=20), we obtained data indicating a significant decrease in the subjective pain score after 20 days of therapy, which amounted to 1.6 ± 0.12 points, as well as a significant stability of this indicator after 90 days from the start of therapy (1.1±0.11 points). A similar significant dynamics of the subjective pain assessment parameter was observed in the compared control group and amounted to
20 days of treatment and 90 days of observation from the beginning of therapy, respectively, 1.9±0.17 and 1.6±0.15 points. However, in a detailed analysis of the subjective assessment of pain in the compared groups, we found a significant decrease in this parameter in the Keltikan ® complex group in comparison with the control group after 20 days of therapy and after 90 days of observation (Fig. 2).


Thus, the data obtained indicate a significant effectiveness of the Keltikan ® complex in reducing the subjective assessment of pain and the stability of this parameter after 90 days of observation in patients suffering from exacerbation of chronic nonspecific pain in the lower back, in comparison with the control group.
We have demonstrated that in patients suffering from exacerbation of chronic nonspecific pain in the lower back, in the 1st and 2nd compared groups, before the start of treatment, there were no significant differences in the parameter comprehensive pain questionnaire(which reflects the impact of pain on the quality of life of patients - ed.), and the total score on the scale was 87.0±2.46 and 87.3±2.74, respectively.
In the 1st group of patients (Keltikan ® complex, n=20), we obtained data indicating a significant decrease in the total score on a comprehensive pain questionnaire, which amounted to 46.5±2.67, as well as a significant stability of this indicator after 90 days from the start of therapy (27.4±2.76 points). Similar significant dynamics of the total score according to the comprehensive pain questionnaire was also noted in the compared control group and amounted to 54.2±2.36 and 33.6±3.14 points, respectively, after 20 days of treatment and 90 days of observation from the start of therapy. However, in a detailed analysis of the total score on a comprehensive pain questionnaire, which reflects the effect of pain on the quality of life in the compared groups, we found a significant decrease in this parameter in the Keltikan ® complex group compared to the control group after 20 days of therapy and after 90 days of observation ( Fig. 3).


Thus, the data obtained indicate
about the significant effectiveness of the Keltikan ® complex in reducing the impact of pain on the quality of life of patients (according to the results of a comprehensive pain questionnaire) suffering from exacerbation of chronic nonspecific pain in the lower back, in comparison with a group of patients who received a set of procedures.
As the results of our study showed, in patients suffering from exacerbation of chronic nonspecific pain in the lower back, in the 1st and 2nd compared groups, there were no significant differences before the start of treatment. for life dysfunctions according to the Oswestry scale, and the indicator was 36.0±0.24 and 36.2±0.23 points, respectively.
In the 1st group of patients (Keltikan ® complex, n=20), we obtained data indicating a significant improvement in life (according to the results of reducing the negative impact of pain on various areas of life) according to the Oswestry questionnaire after 20 days of therapy; this indicator was 17.3±1.12 points, as well as significant stability of this indicator after 90 days from the start of therapy (8.6±0.71 points). A similar significant change in the parameter of improvement in vital activity was also noted in the compared group and amounted to 21.4±1.17 and 12.7±0.89 points after 20 days of treatment and 90 days of observation from the start of therapy, respectively.
It is important to note that in a detailed analysis of the data obtained, we found a significant improvement in this indicator in the Keltikan ® complex group compared with the control group after 20 days of therapy and after 90 days of observation (Fig. 4).


Thus, the data obtained indicate
about the significant effectiveness of the Keltikan ® complex in improving life (according to the results of reducing the negative impact of pain on various areas of life) in patients suffering from exacerbation of chronic nonspecific pain in the lower back, in comparison with the group of patients who received a set of procedures.
When evaluating security of the drug Keltikan ® complex in the group of patients taking Keltikan ® complex with exacerbation of chronic nonspecific pain in the lower back, there were no cases of adverse drug reactions, which indicates its safety.

conclusions

Finally It should be noted that the use of physiological pyrimidine nucleotides is justifiably considered one of the promising directions in the treatment of exacerbations of chronic nonspecific pain in the lower back. While taking the Keltikan ® complex, the regeneration of the nervous tissue is enhanced, the processes of nerve impulse conduction are normalized, the severity of the pain syndrome is significantly reduced and the quality of life is improved, which makes it possible to recommend the Keltikan ® complex as an addition to analgesic therapy for this category of patients.

Literature

1. Rachin A.P., Anisimova S.Yu. Dorsopathy: an actual problem of a practicing doctor // BC. 2012. V.20. No. 19. pp.964–967.
2. Rachin A.P., Yakunin K.A., Demeshko A.V. Myofascial pain syndrome. Ser. "Actual Issues of Medicine". M., 2009 .
3. Rachin A.P. Patterns of the formation of chronic headache (clinical, psychophysiological and social factors), optimization of therapy, prognosis and prevention. Dis. … Dr. med. Sciences. PMGMU them. THEM. Sechenov. M., 2007 .
4. Rachin A.P., Yudelson Ya.B. Chronic daily headache in golovnaya bol "u detej // Z. nevrologii i psihiatrii im. C.C. Korsakova. 2005. V.105. No. 1. S.83–85 children // Journal of Neurology and Psychiatry named after C.C. Korsakov. 2005. T. 105. No. 1. P. 83–85.
5. Rachin A.P., Yudelson Ya.B., Sergeev A.V. Functional features of the brain (according to the dynamics of the P300 potential) in the process of chronic tension-type headache // Pathogenesis. 2005. No. 1. P.48.
6. Yudelson Ya.B., Rachin A.P. Features of tension headache in children and adolescents // Questions of modern pediatrics. 2003. V.2. No. 5. P.51.
7. Yudelson Ya.B., Rachin A.P. Clinical and psychological characteristics of tension headache in children and adolescents // Neurological journal. 2003. No. 5. pp.32–35.
8. Rachin A.P., Sergeev A.V. Persen: possibilities of application in anxiety disorders and sleep disorders // Farmateka. 2008. No. 8. pp.29–32.
9. Rachin A.P., Mikhailova E.V. Depressive and anxiety states. Ser. "Library of a specialist doctor". Psychiatry. Neurology. General medical practice. M., 2010 .
10. Rachin A.P. Therapy of sleep disorders: classification and analytical approaches // Handbook of a polyclinic doctor. 2007. No. 6. pp.64–68.
11. Rachin A.P., Yudelson Ya.B. Evidence-based pharmacoanalytics of osteoarthritis therapy // Farmateka. 2007. No. 19. From 81 .
12. Yudelson Ya.B., Rachin A.P., Belogorokhov O.O. Efficacy and safety of the drug neurodiclovit in dorsalgia // Farmateka. 2008. No. 20. pp.132–136.
13. Karelov A.E., Zakharov D.A., Lebedinsky K. M., Semenov D.A. New technologies in anesthesiology: purine analgesia // Bulletin of St. Petersburg. university 2008. No. 11 (1). pp.77–82.
14. Salter M.W., Henry J.L. Effects of adenosine 5'-monophosphate and adenosine 5'-triphosphate on functionally identified units in the cat spinal dorsal horn. Evidence for a differential effect of adenosine 5’-triphosphate on nociceptive vs non-nociceptive units // Neurosci. 1985 Vol. 15. P.815–825.
15. Phillis J.W., Kirkpatrick J.R. The actions of adenosine and various nucleosides and nucleotides on the isolated toad spinal cord // Gen. Pharmacol. 1978 Vol. 9. P.239–247.