Myoclonus is defined as
shock-like, brief involuntary
abnormal movements in muscle jerking caused by external stimuli; and it arises from
progressive myoclonus epilepsy, post-
anoxic encephalopathy and
Alzheimer's disease, causing disabling symptoms. It is a rare syndrome but very difficult to control.
Piracetam (2-oxo-1-pyrrolidineacetamide, Myocalm) was developed more than 30 years ago as a cyclic derivative of
gamma-aminobutyric acid (
GABA); it has been used in European countries for the treatment of
memory loss and other cognitive defects in patients. Some reports have suggested that
piracetam has anti-
myoclonus activities, but the mechanisms of
myoclonus are not well-identified, and thus there have been few preclinical studies on
piracetam for the treatment of
myoclonus. We investigated the effect of
piracetam and
clonazepam, an anti-epileptic
drug, on high dosage
urea-induced
myoclonus using an electromyogram in rats. The incidence of
myoclonus induced by
urea 4.5 g/kg (i.p.) was significantly reduced by
piracetam at 300 mg/kg (i.p.) and by
clonazepam at 0.3 mg/kg (p.o.). The coadministration of
piracetam 100 mg/kg (i.p.) and
clonazepam at 0.03-0.1 mg/kg (p.o.) significantly reduced the incidence of
myoclonus, although separate administration was not effective. After
oral administration of
piracetam, it is rapidly and completely absorbed and excreted almost unchanged in the urine; however, it does show a little binding to human
serum protein. Repeated
oral administration of
piracetam for 7 days in phase-I trials did not show any accumulation of the
drug. In the placebo-controlled double-blind crossover trial of
piracetam conducted in the UK, there was a significant improvement in cortical
myoclonus. In phase-II trials,
piracetam inhibited
myoclonus and showed an improvement in the quality of life (QOL) of the patients. These results show that
piracetam has a beneficial use in clinics for severe
myoclonus patients when it is combined with anti-epileptic drugs, demonstrating an improvement in the
myoclonus and QOL of patients.