Evidence for synergism between the antimyoclonic actions of 5-hydroxytryptophan and clonazepam in rats

The protective effect of the precursor of 5-hydroxytryptamine (5-HT), 5-hydroxytryptophan (5-HTP) against myoclonus induced in rats by picrotoxin and allyglycine was demonstrated. The inhibition by 5-HTP of picrotoxin-induced myoclonic movements was found to correlate well with an increased 5-HT release from the cerebral cortex. p-Chlorophenylalanine (PCPA) pretreatment aggravated the actions of both picrotoxin and allyglycine by shortening their myoclonic latencies. These findings suggest that there is an antimyoclonic effect of 5-HT in the brain. The protective effect of clonazepam against these two myoclonic models was found to be potentiated in 5-HTP-pretreated animals. Only a partial inhibition of its protective effect resulted from PCPA pretreatment. These data suggest that a beneficial synergism is likely to occur between 5-HTP and clonazepam for the inhibition of myoclonus and that a 5-HTergic mechanism does not play a significant role in the antimyoclonic action of clonazepam.