Lack of effect of amitriptyline in murine myotonia

Amitriptyline, a tricyclic antidepressant, has been reported to diminish signs of human myotonic muscular dystrophy, but has not been examined in other myotonias. Normal and myotonic (ADRmto) mice were injected acutely with either amitriptyline, phenytoin, procainamide or 0.9% saline. In addition, two groups of myotonic mice were injected chronically with either 0.9% saline or amitriptyline for 28 days. Behavior, assessed before injection using a "drop test," was re-evaluated at 30-min intervals for up to 180 min postinjection, as well as at the end of the 28-day chronic trial. If improvement in behavior was noted, the mice were then evaluated with insertional needle electromyography (EMG) and in vitro contractility (maximal tetanic tension and relaxation time) studies. Neither acute nor chronic amitriptyline administration had any beneficial effect on behavior, EMG or contractile parameters in myotonic mice. Phenytoin abolished abnormal EMG activity and improved behavior. Procainamide improved behavior and contractility parameters but had no effect on EMG. These results confirm that the myotonic mouse is responsive to classic antimyotonic agents, but not to amitriptyline.