[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.

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).

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.

Rapid simultaneous determination of eperisone, tolperisone, and tizanidine in human serum by using a MonoSpin® C18 extraction column and liquid chromatography/tandem mass spectrometry.

A method was developed for rapid toxicological analysis of eperisone, tolperisone, and tizanidine in human serum using a MonoSpin® C18 extraction column and LC/MS/MS. The method was validated for LOD, linearity, precision, and extraction recovery. This method was rapid with an LOD of 0.5 ng/mL, linearity range 1-500.0 ng/mL (r2 = 0.999), and RSD value below 14.6%. Extraction recovery from the sample was greater than 98.6, 98.8, and 88.5% for eperisone, tolperisone, and tizanidine, respectively. Results showed that combination of the MonoSpin C18 extraction column and LC/MS/MS is a simple and rapid method for the analysis of these three analytes, and a method is described for simultaneous quantitative determination of the analytes in human serum by LC/MSIMS. This method was used to determine the serum levels of eperisone in a patient with eperisone poisoning, and could be successfully applied for screening analyses in clinical cases other than poisoning.

[Mydeton: a centrally acting muscle relaxant drug from Gedeon Richter LTD]. / Mydeton: a Richter centrális támadáspontú izomrelaxánsa.

Since its introduction in 1959 tolperisone hydrochloride (Mydeton) is still one of the leading products of Gedeon Richter Ltd. It has been successfully applied for treating different painful muscle spasms. The compound is successfully marketed also by several foreign, mostly Japanese, pharmaceutical companies, as a central muscle relaxant agent. The present summary overviews the pharmacology of tolperisone, with special emphasize on its still partly understood way of action. Data from the scientific literature as well as our own experimental results strongly support the hypothesis that inhibition of voltage gated sodium channels is a major component of the mechanism of action of tolperisone. The paper also summarizes the clinical results with tolperisone and the perspectives of the therapeutic use of centrally acting muscle relaxants.