Chlormethiazole and dizocilpine block the behavioural, but not the neurotoxic effects of 5,7-dihydroxytryptamine in mice.
Intracerebroventricular administration to mice of 5,7-dihydroxytryptamine at a dose of 300 micrograms resulted in convulsive behaviour and death (latency 7.6 +/- 1.7 min.). Pretreatment with dizocilpine or chlormethiazole resulted in a dose dependent inhibition of the convulsive behaviour. A dose of dizocilpine of 0.12 mumol/kg or chlormethiazole at a dose of 150 mumol/kg prevented seizures for 30 min. Injection of 5,7-dihydroxytryptamine (75 micrograms, intracerebroventricularly) produced an approximate 50% neurotoxic loss of cerebral 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) 8 days later. This loss was not prevented by administration of either dizocilpine (4.5 mumol/kg intraperitoneally) or chlormethiazole (300 mumol/kg intraperitoneally) given 5 min. before and 55 min. after the 5,7-dihydroxytryptamine injection. It is proposed that chlormethiazole and dizocilpine may protect against 5,7-dihydroxytryptamine-induced seizures because of their anticonvulsant activity, but that they do not prevent the neurotoxic effects of the compound. The data also suggest that the neurotoxic effects of substituted amphetamines such as 3,4-methylene dioxymethamphetamine (MDMA or Ecstasy) do not result from the formation of a 5,7-dihydroxytryptamine like compound.
Snape
M F
MF
Astra Neuroscience Research Unit, London, U.K.
Colado
M I
MI
Green
A R
AR
D015116:5,7-Dihydroxytryptamine / Q000037:antagonists & inhibitors*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002719:Chlormethiazole / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012701:Serotonin / Q000378:metabolism
D002719:Chlormethiazole; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016291:Dizocilpine Maleate