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 allylglycine 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 allylglycine 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.
Paul
V
V
Department of Pharmacology, University of Madras, India.
Krishnamoorthy
M S
MS
D006916:5-Hydroxytryptophan / Q000627:therapeutic use*; D000501:Allylglycine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002998:Clonazepam / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D009207:Myoclonus / Q000139:chemically induced / Q000517:prevention & control*; D010852:Picrotoxin; D051381:Rats; D013997:Time Factors
D006916:5-Hydroxytryptophan; D000501:Allylglycine; D002998:Clonazepam; D010134:Fenclonine; D010852:Picrotoxin