Enhancement by alpha-fluoromethylhistidine of the thiopental sleep-prolonging action of delta 9-tetrahydrocannabinol.
The effect of alpha-fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, on the potentiation of thiopental-induced sleep by delta 9-tetrahydrocannabinol (THC), which inhibits the histamine turnover in the brain, was examined in mice and rats. The sleeping time after injection of thiopental sodium (40 mg/kg, IV) was prolonged by THC (10 mg/kg, IP, 1 h before) to approximately twice the control value. alpha-FMH (50 mg/kg, IP) administered alone had no significant influence on the thiopental sleeping time. However, alpha-FMH given 1 or 3 h before THC treatment markedly enhanced the THC potentiation of thiopental-induced sleep. Such an enhancement by alpha-FMH was not observed when alpha-FMH was administered 15 h before THC treatment. The brain histamine level decreased by 60% during the first 4 h after alpha-FMH injection and remained low until 15 h after the treatment. The thiopental sleep-potentiating action of morphine, chlorpromazine and diazepam was not affected by pretreatment with alpha-FMH. The transient enhancing effect of alpha-FMH on the THC potentiation of thiopental-induced sleep suggests that the histaminergic system is one of the activating transmitter systems in the brain.
Oishi
R
R
Department of Pharmacology, Okayama University Medical School, Japan.
Itoh
Y
Y
Nishibori
M
M
Saeki
K
K
Ueki
S
S
D000818:Animals; D001921:Brain / Q000378:metabolism; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D013759:Dronabinol / Q000494:pharmacology*; D004357:Drug Synergism; D006632:Histamine / Q000378:metabolism; D006639:Histidine / Q000031:analogs & derivatives*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D012890:Sleep / Q000187:drug effects*; D013874:Thiopental / Q000494:pharmacology*
D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D013759:Dronabinol; D006632:Histamine; D002262:Carboxy-Lyases; D006640:Histidine Decarboxylase; D013874:Thiopental