Inhibition of sleep and benzodiazepine receptor binding by a beta-carboline derivative.
The effects of systemic injections of beta-carboline-3-carboxylate-t-butyl ester (beta-CCtB) were investigated with regard to normally occurring sleep and several measures of benzodiazepine receptor occupancy in rats. A dose of 30 mg/kg of beta-CCtB was found to have a long time-course of action as measured by an in vivo assay for benzodiazepine binding, with an 84% depletion of [3H]diazepam binding at one hour after the intraperitoneal injection. This dose of beta-CCtB was shown to delay sleep onset, decrease non-REM and total sleep in the first two hours after the injection, and to delay the appearance of REM sleep after the sleep onset. The dose- and time-dependence of the effects on sleep approximated the dose- and time-dependence of inhibitory effects of an IP injection of beta-CCtB on in vitro measures of benzodiazepine receptor affinity and number.
Martin
J V
JV
Department of Biology, Rutgers University, Camden, NJ 08102.
Cook
J M
JM
Hagen
T J
TJ
Mendelson
W B
WB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D058787:GABA-A Receptor Antagonists; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors
D002243:Carbolines; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; C043232:tert-butyl beta-carboline-3-carboxylate; D003975:Diazepam