Tolperisone has been evaluated and found to be effective for the treatment of several musculoskeletal disorders like, cervicobrachial myofascial pain syndrome, post-stroke spasticity, back pain, multiple sclerosis, vertebrogenic algesic syndromes, neuroleptic syndrome, neurolathyrism, neurosensory hypoacusis, painful reflex muscle spasm, muscular and vascular complaints accompanying climacterics. It is also used as an adjuvant to complex therapy, in 300 to 450 mg daily doses, for the treatment of locomotor diseases accompanied by muscular hypertonia, muscular spasticity, and contracture [2
Tolperisone, a centrally acting muscle relaxant (CMR) free from side effects, first described by Nador and Porszasz in 1958, is a clinically useful drug for relieving spasticities of neurological origin and muscle spasms associated with painful locomotor diseases. Its first description classified it as an antinicotinic drug based on the fact that it effectively inhibited nicotine induced lethality. Nevertheless, it also inhibited convulsions evoked by electroshock, pentylenetetrazole or strychnine. Its most characteristic effect, however, is potent inhibition of mono and polysynaptic spinal reflexes, and Ono et al. [13
] reported that a "membrane stabilizing" effect may underlie its pharmacological actions. Tolperisone acts as an acute blocker of voltage dependent sodium channels.
Several randomized controlled clinical trials have demonstrated that Tolperisone has superior efficacy as compared to placebo in the treatment of spastic hypertonia following cerebral stroke [6-8
]. In this indication an individual dose titration which may exceed the recommended maximum dose of 450 mg daily results in optimized therapeutic benefit [6-8
The skeletal muscle relaxant and analgesic activity of Tolperisone has been evidenced in experimental jaw-muscle pain [9
]. When used as prophylactic, Tolperisone reduced isometric force in post-exercise muscle soreness [5
Adverse events experienced were less with Tolperisone as compared to placebo and were mostly of mild-to-moderate intensity. Tolperisone has a good tolerability and no withdrawals caused by adverse events with Tolperisone [6-9,11
]. Single and repeated doses of Tolperisone hydrochloride 150 mg showed that Tolperisone hydrochloride, although being a centrally active muscle relaxant, does not cause any sedation and does not impair reaction times [4
Skeletal muscle relaxant activity of oral Tolperisone has been evaluated in a prospective, randomized, double-blind, placebo-controlled in the treatment of painful reflex muscle spasm associated with diseases of the spinal column or proximal joints. In this study a total of 138 patients, aged between 20 and 75 years, were enrolled in 8 rehabilitation centers. Patients were randomized to receive either 300 mg Tolperisone hydrochloride or placebo for a period of 21 days. Both treatment groups recovered during the 3 weeks rehabilitation program. However, Tolperisone hydrochloride proved to be significantly superior to placebo treatment. (p
= 0.03) [2
TC, a natural glycoside is a centrally acting skeletal muscle relaxant used in the management of low back pain. In clinical trial conducted in Indian population, it was found that Tolperisone was slightly more effective and scored significantly better than TZ [10
]. Another study showed that TC was at least as effective as TZ in the treatment of acute LBP, while it appears devoid of any sedative effect in contrast to TZ [12
]. Hence TC being a commonly used skeletal muscle relaxant was used as the comparator in this study.
Our results demonstrate that Tolperisone is an effective muscle relaxant agent with efficacy similar to that of other compounds, such as TC, which are currently used in the management of low back pain due to a spinal muscles spasm. The results to this study showed that Tolperisone 150 mg provides a better clinical response rates and symptom control over TC 8 mg in patients with acute low back pain with spinal muscle spam. This could be explained by the fact that Tolperisone acts by more than one mechanism: inhibiting the pathologic mono- and polysynaptic reflex activity in the formation reticularis and spinal cord and by stabilizing the nerve membrane. Moreover Tolperisone has analgesic activity in humans, which could be attributed to its chemical structure, the tertiary aryl amine producing a Lidocaine like activity of stabilizing nerve membranes.
The score differences in Laseague's maneuver, pain at rest for both day 3 and day 7 and pain on movement for day 7, showed significantly better results in Tolperisone group. Other muscle spasm assessment parameters also showed better improvement in Tolperisone; however not statistically significant for both day 3 and day 7. The limitations of the study may be was short follow-up and absence of a control group. The need of rescue medication was significantly greater in TC group than that of in Tolperisone group. Global impression on efficacy by doctors and tolerability by patients show significant differences at the end of the study (p < 0.001) the adverse events profile was similar to that documented in earlier studies.
Another consistent advantage of Tolperisone over TC and other muscle relaxant agents is represented by tolerance; in this study, the adverse events were mild to moderate in intensity. On global assessment of tolerability 91.87% of the patients graded Tolperisone as good to excellent. This could be because unlike other centrally acting skeletal muscle relaxants, it has no substantial affinity to adrenergic, cholinergic, dopaminergic or serotonergic receptors in the central nervous system.