Benzodiazepine sensitivity in normal human subjects.
Increasing intravenous doses of diazepam or placebo were administered to ten healthy normal volunteers, and the changes in saccadic eye velocity, self-rated sedation and anxiety, and plasma cortisol and growth hormone concentrations were measured. Diazepam administration (4.4 to 140 micrograms/kg, cumulative dose) resulted in a dose-dependent decrease in saccadic eye velocity and plasma cortisol level as well as a dose-dependent increase in self-rated sedation and plasma growth hormone level. Self-rated anxiety was unaffected in these relatively nonanxious subjects. The diazepam-induced changes in saccadic eye velocity, sedation, and growth hormone and cortisol levels were highly correlated with each other and with increasing plasma diazepam concentration. These results are consistent with a benzodiazepine receptor-mediated action of diazepam. The highly quantifiable and dose-dependent decrease in saccadic eye velocity by benzodiazepines should make this a useful measure of benzodiazepine receptor sensitivity in humans.
Hommer
D W
DW
Matsuo
V
V
Wolkowitz
O
O
Chrousos
G
G
Greenblatt
D J
DJ
Weingartner
H
H
Paul
S M
SM
D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood / Q000494:pharmacology*; D001007:Anxiety / Q000523:psychology; D001288:Attention / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003975:Diazepam / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects; D005133:Eye Movements / Q000187:drug effects*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007263:Infusions, Parenteral; D008297:Male; D008568:Memory / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects*; D012107:Research Design / Q000379:methods; D012438:Saccades / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D013006:Growth Hormone; D003975:Diazepam; D006854:Hydrocortisone