Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone.

Tolperisone, a muscle relaxant used for post-stroke spasticity, is metabolized to its main metabolite by CYP2D6 and to a lesser extent by CYP2C19 and CYP1A2. We investigated the effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on tolperisone pharmacokinetics. A 150 mg oral dose of tolperisone was given to 184 healthy Korean subjects and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 3.14-fold significant increase in AUC0-∞ was observed in the CYP2D6*10/*10 group compared with the CYP2D6*wt/*wt group, whereas a 3.59-fold increase in AUC0-∞ was observed in CYP2C19PMs compared to CYP2C19EMs. Smokers had a 38.5% decrease in AUC0-∞ when compared to non-smokers. When these effects were combined, CYP2D6*10/*10-CYP2C19PM-Non-smokers had a 25.9-fold increase in AUC0-∞ compared to CYP2D6*wt/*wt-CYP2C19EM-Smokers. Genetic polymorphisms of CYP2D6 and CYP2C19 and cigarette smoking independently and significantly affected tolperisone pharmacokinetics and these effects combined resulted in a much greater impact on tolperisone pharmacokinetics.

Effects of CYP2D6*10 allele on the pharmacokinetics of tolperisone.

Tolperisone, a muscle relaxant used for post-stroke spasticity, has been reported to have a very wide interindividual pharmacokinetic variability. It is metabolized mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. CYP2D6 is a highly polymorphic enzyme, and CYP2D6*wt/*wt, CYP2D6*wt/*10 and CYP2D6*10/*10 genotypes constitute more than 90% of the CYP2D6 genotypes in the Korean population. Thus, effects of the CYP2D6*10 on tolperisone pharmacokinetics were investigated in this study to elucidate the reasons for the wide interindividual variability. Oral tolperisone 150 mg was given to sixty-four healthy Koreans, and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CYP2D6*10/*10 and CYP2D6*wt/*10 groups had significantly higher Cmax and lower CL/F values than the CYP2D6*wt/*wt group. The AUCinf of CYP2D6*10/*10 and CYP2D6*wt/*10 groups were 5.18-fold and 2.25-fold higher than the CYP2D6*wt/*wt group, respectively. There were considerable variations in the Cmax and AUC values within each genotype group, and the variations were greater as the activity of CYP2D6 decreased. These results suggest that the genetic polymorphism of CYP2D6 significantly affected tolperisone pharmacokinetics and factor(s) other than CYP2D6 may also have significant effects on the pharmacokinetics of tolperisone.

Effects of CYP2C19 genetic polymorphism on the pharmacokinetics of tolperisone in healthy subjects.

Tolperisone hydrochloride is a centrally-acting muscle relaxant used for relieving spasticities of neurological origin and muscle spasms associated with painful locomotor diseases. It is metabolized to the inactive metabolite mainly by CYP2D6 and, to a lesser extent, by CYP2C19 and CYP1A2. In our previous study, the pharmacokinetics of tolperisone was significantly affected by the genetic polymorphism of CYP2D6, but the wide interindividual variation of tolperisone pharmacokinetics was not explained by genetic polymorphism of CYP2D6 alone. Thus, we studied the effects of CYP2C19 genetic polymorphism on tolperisone pharmacokinetics. Eighty-one subjects with different CYP2C19 genotypes received a single oral dose of 150 mg tolperisone with 240 mL of water, and blood samples were collected up to 12 h after dosing. The plasma concentration of tolperisone was measured by a liquid chromatography-tandem mass spectrometry system. The CYP2C19PM group had significantly higher Cmax and lower CL/F values than the CYP2C19EM and CYP2C19IM groups. The AUCinf of the CYP2C19PM group was 2.86-fold and 3.00-fold higher than the CYP2C19EM and CYP2C19IM groups, respectively. In conclusion, the genetic polymorphism of CYP2C19 significantly affected tolperisone pharmacokinetics.

The Acute Antiallodynic Effect of Tolperisone in Rat Neuropathic Pain and Evaluation of Its Mechanism of Action.

Current treatment approaches to manage neuropathic pain have a slow onset and their use is largely hampered by side-effects, thus there is a significant need for finding new medications. Tolperisone, a centrally acting muscle relaxant with a favorable side effect profile, has been reported to affect ion channels, which are targets for current first-line medications in neuropathic pain. Our aim was to explore its antinociceptive potency in rats developing neuropathic pain evoked by partial sciatic nerve ligation and the mechanisms involved. Acute oral tolperisone restores both the decreased paw pressure threshold and the elevated glutamate level in cerebrospinal fluid in neuropathic rats. These effects were comparable to those of pregabalin, a first-line medication in neuropathy. Tolperisone also inhibits release of glutamate from rat brain synaptosomes primarily by blockade of voltage-dependent sodium channels, although inhibition of calcium channels may also be involved at higher concentrations. However, pregabalin fails to affect glutamate release under our present conditions, indicating a different mechanism of action. These results lay the foundation of the avenue for repurposing tolperisone as an analgesic drug to relieve neuropathic pain.

Risk factors of anaphylaxis in Korea: Identifying drug-induced anaphylaxis culprits using big data.

Drug-induced anaphylaxis is a fatal medical condition whose incidence has been increasing continuously. Due to differences between genetic backgrounds and health care systems, different populations may be prone to various causative drugs. Using the Health Insurance Service and Assessment Service database, we investigated culprit drugs for drug-induced anaphylaxis and common medication risk factors in the Korean general population. We collected medical prescription histories within 3 days prior to anaphylaxis between January 2011 and December 2019 from the HIRA database. Designed as a case-crossover study, the attributable visits (case visits) were matched to medical visits (control visits) with the drug sets for each visit. We collected a list of medication risk factors for anaphylaxis and calculated the risk ratio of each agent using the chi-square test and conditional logistic regression analysis. A total of 159,473 individuals were listed in the database with a diagnosis of anaphylaxis in the HIRA from 2011 to 2019. After evaluating the suitability of control visits for matching with a case visit, 8168 subjects and 767 drugs were analyzed. The chi-square analysis identified 31 drugs as potential risk factors for drug-induced anaphylaxis in Korea. After applying a conditional logistic regression analysis for each agent, 5 drugs were found to be the common medication risk factors for drug-induced anaphylaxis: cefaclor, iopromide, iohexol, iomeprol, and tolperisone. We found 5 medication risk factors that showed the highest risk of drug-induced anaphylaxis and their degree of risk using an objective methodology in the Korean general population.

Sensitive and selective LC-MS/MS for the determination of tolperisone and etodolac in human plasma and application to a pharmacokinetic study.

Tolperisone and etodolac were proven to have synergistic effect for patients of acute low back pain associated with musculoskeletal spasm. In this work, a specific, highly sensitive and reproducible analytical method was developed and validated for the simultaneous determination of tolperisone and etodolac in human plasma using liquid chromatography-tandem mass spectrometric technique. Liquid-liquid extraction was optimized for sample preparation. Zorbax C8 column (3.5 µm, 50 × 4.6 mm) was used, carrying a mobile phase mixture of 10.0 mM ammonium formate:acetonitrile (40:60, v/v) pH 3.8, running in an isocratic mode. Chlorzoxazone acted as an internal standard. Sample volume of injection was 5.0 µL, and analysis was achieved within 2.5 min. Detection and quantitation were performed by electrospray ionization mass spectrometry using the multiple-reaction monitoring mode. The proposed method could determine the analytes in the range of concentration 0.5-200.0 ng mL-1 for tolperisone and 0.05-20.0 µg mL-1 for etodolac. Findings of inter- and intraday precisions were ≤12.3% with accuracy of ±5.0%. Pharmacokinetics study for the two drugs after oral administration of healthy human volunteers was achieved with the aid of application of the developed study.

RESUME-1: a Phase III study of tolperisone in the treatment of painful, acute muscle spasms of the back.

Tolperisone is a nonopioid, centrally acting muscle relaxant in clinical development in the USA for the treatment of symptoms associated with acute, painful muscles spasms of the back. CLN-301, RESUME-1, is a 14-day double-blind, randomized, placebo-controlled, parallel-group Phase III study of the efficacy and safety of tolperisone administered orally three-times daily in 1000 male and female subjects at approximately 70 clinical sites in the USA experiencing back pain due to or associated with muscle spasm of acute onset. Tolperisone is a promising therapeutic for managing acute, painful muscle spasms of the back as it appears to lack the off-target CNS effects often seen with conventional skeletal muscle relaxants. Clinical Trials registration number: NCT04671082.

[Efficiency of the application of miorelaxants in lower cross myofascial syndrome]. / Effektivnost' primeneniya miorelaksantov pri nizhnem perekrestnom sindrome.

OBJECTIVE: To evaluate the efficacy of the drug Tolperisone (Calmirex) in patients with inferior cross syndrome against the background of standard therapy. MATERIAL AND METHODS: The study involved male and female patients aged 25-55 years with inferior cross syndrome. The main research method was clinical, which was supplemented by biomechanical examination and the use of scales and questionnaires (VAS, Oswestry, McGill). RESULTS AND CONCLUSION: The effectiveness of the use of muscle relaxants in the treatment of the lower cross syndrome has been studied and proved with the identification of the most reliable and effective methods for correcting this pathology. The effectiveness of the use of muscle relaxants in the treatment of lower cross syndrome was studied, with the identification of the most reliable and effective methods for correcting this pathology. The presented clinical study of biomechanical and statodynamic disorders of the musculoskeletal system in myofascial pain syndromes, taking into account the peculiarities of the lesion of the sanogenetic and pathogenetic region, will be useful in prescribing personalized treatment not only for neurologists, but also for primary care physicians, chiropractors, osteopaths, rheumatologists and rehabilitologists.

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study.

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

[Medical adherence as the basis for effective therapy - current state of the art]. / Priverzhennost' lecheniyu kak klyuchevoi faktor povysheniya effektivnosti konservativnoi terapii.

OBJECTIVE: The study was to assess the importance of the problem of medical adherence (MA) among therapists in St. Petersburg (2021). MATERIAL AND METHODS: The study involved 96 doctors of various therapeutic specialties (neurologists, therapists and rheumatologists), who were asked to respond to an original questionnaire concerning MA, that was designed in neurology department of Military Medical academy n.a. S.M. Kirov, St. Petersburg It was found that, according to experts, the main negative factors that significantly decreases MA are the high cost of the drug (40.1%) and polypharmacy (22.1%); the main property of the drug associated with high MA is the convenience of taking it - once a day (51.1%). Such drugs include, for example, a new form of the muscle relaxant tolperisone hydrochloride prolonged release 450 mg. RESULTS AND CONCLUSIONS: According to experts, the main negative factors that significantly reduce MA are the high cost of the drug (40.1%) and polypharmacy (22.1%); the main property of the drug associated with high MA on the part of patients is the convenience of its administration - 1 once a day (51.1%). Such drugs include, for example, a new form of release of the muscle relaxant tolperisone hydrochloride prolonged release 450 mg. CONCLUSIONS: A systematic approach is required to improve MA, carried out both at the state level (changing public consciousness, financing systems, etc.) and in tandem doctor-patient (moving away from paternalistic medicine, prescribing depot forms of drugs, etc.).

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

[Pain, emotion, cognition. Pathogenetic relationships and effects of therapy with nonsteroidal anti-inflammatory drugs]. / Bol', emotsii i kognitsii. Patogeneticheskie vzaimosvyazi i effekty terapii nesteroidnymi protivovospalitel'nymi preparatami.

OBJECTIVE: To study the dynamics of pain intensity in comparison with changes in the severity of depression and cognitive deficits when using non-steroidal anti-inflammatory drugs and/or central muscle relaxants in patients with chronic non-specific back pain. MATERIAL AND METHODS: Sixty patients (26 men and 34 women), aged 42 to 59 years, with chronic non-specific back pain were examined. All patients were divided into three groups. In the first group, dexketoprofen was used at a dose of 75-100 mg per day for 10 days. Patients of the second group received dexketoprofen according to a similar scheme, as well as tolperisone (200-450 mg per day) for 30 days. Patients of the third group took diclofenac sodium (100 mg per day) for 10 days. The intensity of pain, its affective component, the severity of asthenic, depressive, anxiety manifestations and cognitive disorders were tested at baseline and on the 10th and 30th days. RESULTS: Pain significantly decreased in all patients, more significantly in the first and second groups. The analgesic effect in the first and third groups was unstable, and the improvements achieved by the last test were partially reduced. In patients of the first and second groups, regression of anxiety and depressive symptoms was observed from day 10 to the end of observation. At the same time, the emotional assessment of pain in patients of the first group decreased by the 10th and increased by the 30th day of observation. By the end of the study, patients of the second group showed positive dynamics of indicators of asthenia and cognitive disorders. CONCLUSIONS: The most effective analgesic therapy using a combination of dexketoprofen and tolperisone was accompanied by a positive dynamics of depressive manifestations and cognitive disorders. The choice of an algorithm for treating pain should take into account the need and possibility of treatment its biological and psychological (affective, cognitive) components.

[The assessment of the clinical efficacy and tolerability of complex treatment of patients with acute low-back pain]. / Otsenka klinicheskoi effektivnosti i perenosimosti kompleksnoi terapii patsientov s ostroi bol'yu v nizhnei chasti spiny.

OBJECTIVE: To compare the efficacy and tolerability of different combinations of domestic generics meloxicam (amelotex), tolperisone (calmirex) and B vitamins (compligam B) in the treatment of acute low-back pain. MATERIAL AND METHODS: Ninety patients with acute low-back pain (ICD-10 M54.5) were studied. Indications and prescribing of the drugs was carried out under the international generic name. Pain was assessed using a visual analog pain scale in mm (VAS). To relieve pain, all patients received the non-steroidal anti-inflammatory drug with a favorable safety profile meloxicam (amelotex). With the aim of optimization, 3 therapy regimens were proposed: group 1 (n=30) received amelotex, calmirex, and B vitamins (compligam B). Group 2 (n=30) received amelotex and calmirex. Group 3 (n=30) was treated with amelotex and compligam B. With a decrease in pain by 50% or more from the baseline level and a VAS <40 mm, patients could reduce the dose of amelotex from 15 to 7.5 mg or stop taking it. RESULTS: During treatment, all groups showed a significant regression of pain according to VAS: in group 1 from 77 to 9 mm, in group 2 from 74 to 12 mm, in group 3 from 69 to 14 mm. The maximum statistically significant reduction in pain and the degree of muscle tone was observed in group 1. Adverse reactions occurred in all groups, but they were weak and transient, and did not require correction or discontinuation of therapy. Only one patient from group 3 had a persistent rise in blood pressure. The average duration of temporary disability was 5.8 days in group 1, 7.4 in group 2, and 9.5 days in group 3. High efficacy and good tolerability of all 3 therapy regimens were noted. The combination of amelotex, calmirex and compligam B received the highest rating in the opinion of doctors and patients. CONCLUSION: All 3 treatment regimens optimize therapy in patients with acute low-back pain, reduce the dose and timing of the NSAID administration as well as the risk of adverse reactions. The results indicate that the combination of amelotex, calmirex and compligam B is a synergy of three pain relief systems due to the effect on different pathogenetic mechanisms, thereby providing the maximum analgesic effect, shortening the course of treatment and duration of temporary disability, reducing the risk of relapse and chronicity of pain.

[The use of myorelaxants in the treatment of chronic non-specific pelvic pain]. / Primenenie miorelaksantov v lechenii khronicheskoi nespetsificheskoi tazovoi boli.

Chronic nonspecific pelvic pain is one of the most pressing problems of modern neurology, due to complex interdisciplinary diagnostic and therapeutic studies. The etiology and pathophysiology of pain syndromes are studied from the point of view of each individual medical specialty, but do not consider the relationship and interaction of pathogenetic factors. In many areas, clinical guidelines for the treatment of chronic pelvic pain have been developed, but without taking into account the multidisciplinary approach to this polyetiological disease. OBJECTIVE: To evaluate the efficacy of tolperisone (calmirex) in patients with chronic nonspecific pelvic pain receiving standard therapy. MATERIAL AND METHODS: In the course of clinical work, 61 patients with chronic nonspecific pelvic pain were observed. To identify the dynamics of the study, all patients were assessed for the severity of pain using a visually analogue scale (VAS), the area of pain, muscle-tonic reactions estimated by the index of muscle tension according to Khabirov. Deviations of the biomechanical parameters of the pelvic region and restoration of the musculoskeletal system statics were evaluated. According to the study protocol, the efficacy of tolperisone (calmirex) was studied in patients receiving standard therapy. RESULTS AND CONCLUSION: Myofascial and muscle-tonic reactions play a significant role in the development and maintenance of chronic nonspecific pelvic pain. At the same time, tolperisone (calmirex) together with standard therapy of chronic nonspecific pelvic pain contributes to an effective regression of pain of myofascial and muscular-tonic origin, and creates a favorable restorative background for non-drug treatment.

An assessment of the centrally acting muscle relaxant tolperisone on driving ability and cognitive effects compared to placebo and cyclobenzaprine.

WHAT IS KNOWN AND OBJECTIVE: Tolperisone is a centrally acting muscle relaxant under development in the United States as a treatment for acute and painful symptoms of muscle spasms. The objective of this three-way, randomized, blinded, three-period crossover study was to assess the safety and cognitive effects of tolperisone compared to placebo and the widely used muscle relaxant cyclobenzaprine in healthy volunteers. METHODS: Subjects were randomized to 1 of 3 treatment arms to receive tolperisone (150 mg), cyclobenzaprine (10 mg) or placebo 3 times per day (TID) in 3 separate study periods. Subjects completed a driving test on the Cognitive Research Corporation's Driving Simulator (CRCDS Mini-Sim), a validated driving simulator, on day 1 at time to maximum plasma concentration, on day 2 before the morning dose of study drug and on day 3 at steady state following the morning dose. Subjects were assessed on various driving parameters and on a computer-administered digit-symbol substitution test (CogScreen symbol digit coding test). The driving scenario is a monotonous 100 km highway route on which subjects are instructed to maintain speed and lane position. RESULTS AND DISCUSSION: The performance of subjects who had received tolperisone was not significantly different from those who had received placebo in terms of the primary end point: standard deviation of lateral position, a measure of weaving. Subjects who had received tolperisone also performed comparably to those who had received placebo on a range of secondary measures assessing driving ability, cognition and psychomotor performance. In contrast, subjects who had received cyclobenzaprine showed significant impairment compared to placebo (P < .01) on the primary end point of standard deviation of lateral position and on the majority of the secondary end points of driving ability. Despite their markedly poorer driving performance after receiving cyclobenzaprine, few subjects reported feeling unsafe to drive on day 1 (10.3%) and day 2 (3.4%). The incidence of adverse events was similar for tolperisone (36.4%) and placebo (29.0%) and was greater for cyclobenzaprine (45.4%). WHAT IS NEW AND CONCLUSION: Subjects who received tolperisone (150 mg TID) experienced no impact on various measures of driving, self-reported sleepiness and cognition measures compared to placebo, in contrast to those who received the widely used muscle relaxant cyclobenzaprine (10 mg TID).

Binding of Tolperisone Hydrochloride with Human Serum Albumin: Effects on the Conformation, Thermodynamics, and Activity of HSA.

Tolperisone hydrochloride (TH) has muscle relaxant activity and has been widely used for several years in clinical practice to treat pathologically high skeletal muscle tone (spasticity) and related pains. The current study was designed to explore the binding efficacy of TH with human serum albumin (HSA) using multispectrscopic, calorimetric approach, FRET, esterase-like activity, and a molecular docking method. A reduction in fluorescence emission at 340 nm of HSA was attributed to fluorescence quenching by TH via a static quenching type. Binding constants ( Kb) were evaluated at different temperatures, and obtained Kb values were ∼104 M-1, which demonstrated moderately strong affinity of TH for HSA. A calculated negative Δ G° value indicated spontaneous binding of TH to HSA. Far-UV CD spectroscopy revealed that the α-helix content was increased after TH binding. The binding distance between donor and acceptor was calculated to be 2.11 nm based on Förster's resonance energy transfer theory. ITC results revealed TH interacted with HSA via hydrophobic interactions and hydrogen bonding. The thermal stability of HSA was studied using DSC, and results showed that in the presence of TH the structure of HSA was significantly more thermostable. The esterase-like activity of HSA showed fixed Vmax and increased Km suggesting that TH binds with HSA in a competitive manner. Furthermore, molecular docking results revealed TH binds in the cavity of HSA, that is, subdomain IIA (Sudlow site I), and that it hydrogen bonds with K199 and H242 of HSA. Binding studies of drugs with HSA are potentially useful for elucidating chemico-biological interactions that can be utilized in the drug design, pharmaceutical, pharmacology, and biochemistry fields. This extensive study provides additional insight of ligand binding and structural changes induced in HSA relevant to the biological activity of HSA in vivo.

[A systematic review of using myorelaxants in treatment of low back pain]. / Sistematicheskii obzor po primeneniiu miorelaksantov pri boli v nizhnei chasti spiny.

A systematic review summarizes the results of studies on the efficacy of myorelaxants (tolperisone, tizanidine, thiocolchicoside or baclofen) in the treatment of acute nonspecific low back pain published up to Dec. 2017. The authors conclude that there are enough data to confirm the efficacy of myorelaxants in treatment of nonspecific low back pain, myorelaxants are recommended as monotherapy or in combination with analgesics or NSAID, the nonsedative drugs tolperisone or thiocolchicoside should be preferred.

Results of the post-registration clinical study "PARUS" on efficiency and safety assessment of Mydocalm-Richter for local injection therapy of a myofascial trigger zone.

AIM: The "PARUS" program included investigation of the analgesic, muscle relaxant and sedative effects of Mydocalm-Richter which acts as central muscle relaxant in patients with myofascial pain syndrome, taking into account its registered indication for use - the hypertonus and cross-striated muscle spasm. MATERIALS AND METHODS: Fifty patients with myofascial trigger points, the mean age of 41.67±11.86 years, have been enrolled in the study. All patients had undergone clinical examination that allowed the diagnosis of myofascial pain syndrome. The intensity of pain syndrome was evaluated using the pain visual analogue scales and McGill pain questionnaire. Visualization of area in spasm and evaluation of blood circulation was carried out using the ultrasound scan of target muscle. In order to objectively evaluate any conceivable hypotensive and sedative effects of Mydocalm-Richter we used the orthostatic test, Schulte's test for attention span and perfor-mance distribution and Munsterberg's test for attention discrimination and concentration. RESULTS: The analgesic and muscle relaxant effects of Mydocalm-Richter become apparent by day 3 post-injection, and the muscle relaxation effect is reaching its maximum on day 10 post-injection. Cardiovascular function following administration of Mydocalm-Richter was evaluated using the orthostatic test which revealed good orthostatic tolerance. Single injection of tolperisone hydrochloride possessing a central muscle relaxant activity has no sedative effect and does not influence patient response time. The ultrasound examination data demonstrated the improvement and in some cases restoration of blood circulation in the myofascial trigger points. CONCLUSION: Clinical study "PARUS" conducted in patients with myofascial pain has demonstrated a positive muscle relaxant and analgesic effect of Mydocalm-Richter that resulted in restoration of peripheral circulation in the myofascial trigger pointsconfirmed by ultrasound examination. An important benefit of this drug product is the absence of sedative effect and arterial hypotension.

[Results of a randomized double blind parallel study on the efficacy and safety of tolpersione in patients with acute nonspecific low back pain]. / Rezul'taty randomizirovannogo dvoinogo slepogo parallel'nogo issledovaniia éffektivnosti i bezopasnosti primeneniia tolperizona u patsientov s ostroi nespetsificheskoi bol'iu v nizhnei chasti spiny.

AIM: To evaluate the efficacy and safety of tolpersione injection and oral formulations combined with NSAID over NSAID monotherapy in acute non-specific low back pain. MATERIAL AND METHODS: In this randomized double blind study 239 patients were included in the per protocol analysis. The first 5 days of treatment, patients received tolpersione or placebo injection which was followed by per os administration of tolpersione/placebo tablet up to 14 days. NSAID diclofenac tablet was used in both groups through the study. Functionality assessed by the Roland Morris Disability Questionnaire (RMDQ) at day 5 was the primary endpoint. Secondary endpoints were RMDQ at other time points, pain level change at rest and on movement assessed by the Visual Analogue Scale (VAS), the Clinical Global Impression of Improvement/Patient Global Impression of Improvement (CGI-I and PGI-I), change in the range of motion assessed by the distance from the fingertips to the floor, period of disability days, relative (%) changes in the daily dose of diclofenac from the 7th to the 14th day of therapy. RESULTS AND CONCLUSION: The primary and secondary endpoints clearly demonstrated the significant superiority of tolpersione added to NSAID monotherapy over NSAID monotherapy. The safety assessment revealed no statistically significant differences between the two groups. Based on the results, tolpersione injection and per os formulations can be considered an effective and safe drugs in the combined therapy for patients with acute nonspecific back pain.