*2.3.5 Dantrolene*

Among the oral dugs, dantrolene is the only one which acts outside the central nervous system [51]. It acts on the inhibition of calcium release from the sarcoplasmic reticulum, so, as a final effect, it reduces in muscle the excitation-coupling reaction between actin and myosin fibres. The documented clinical effects are a reduction of muscle tone and phasic reflexes, reduction of spasm, and an increased range of passive motion. Unfortunately, a frequent occurrence of side effects is described with this drug, such as gastrointestinal symptoms, weakness, and sedation although this is less than that seen with other treatments. Over all, a serious side effect with the use of dantrolene is hepatotoxicity, which occurs frequently [51]. In patients with spasticity due to cerebral lesions, dantrolene is the only drug with evidence of efficacy, so from a pure clinical point of view, this is very disappointing. In fact, dantrolene in approved in patients with stroke, cerebral palsy,

traumatic brain injuries, and spinal cord lesions. As shown for baclofen, also for dantrolene, there are many evidences of efficacy and safety of its antispastic effect proven vs. placebo, but no studies focused on functional changes in activities of daily living. It's notable that dantrolene is also used to prevent muscle stiffness and spasms caused by malignant hyperthermia (a rapid rise in body temperature and severe muscle contractions) that can occur during surgery with certain types of anaesthesia [52].
