[A pharmacological profile of piracetam (Myocalm), a drug for myoclonus].
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.
Tajima
K
K
Taiho Pharmaceutical Co., Ltd., Tokyo, Japan.
Nanri
M
M
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D002998:Clonazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D009207:Myoclonus / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D018697:Nootropic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D010889:Piracetam / Q000493:pharmacokinetics / Q000627:therapeutic use; D011788:Quality of Life; D013577:Syndrome; D014508:Urea / Q000009:adverse effects
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D002998:Clonazepam; D014508:Urea; D010889:Piracetam