Effects of tizanidine in healthy volunteers: double-blind study compared with diazepam and a placebo.

Since an experiment in monkeys showed that tizanidine (DS 103-282), a centrally-acting muscle relaxant, has a certain amount of reinforcing property, a double-blind comparative study using questionnaires was carried out in 12 healthy volunteers to investigate the subjective effects of the drug as a measure of its psychic dependence potential using diazepam and a placebo. The dosages of tizanidine were 3 mg and 6 mg and that of diazepam was 10 mg. Neither the maximal clinical dosage of tizanidine (3 mg) nor twice that dosage (6 mg) induced any marked somatic or psychic symptoms compared with the placebo. On the other hand, diazepam 10 mg induced symptoms at a significantly higher incidence than the placebo and tizanidine; i.e., many of those given diazepam mentioned experiencing such symptoms of central nervous system depression as drowsiness and absent-mindedness. With diazepam the volunteers gave positive answers to some items which are regarded as direct parameters of psychic dependence; e.g., one noted that the drug effects were "desirable", two indicated a "euphoric feeling", and five noted a "drunken feeling". Influence on tapping, blood pressure, etc., were observed in the tizanidine 6 mg group in the same extent as in the diazepam group. The blood concentration of tizanidine 6 mg was about four times as high as tizanidine 3 mg. These results indicate that tizanidine is very unlikely to have psychic-dependence potential because of a lack of observable subjective effects and thus, it was concluded that there is little possibility of the drug being abused.