Effects of flunitrazepam on memory and their reversal by two antagonists.
The amnestic effects of flunitrazepam (2 mg intravenously) were studied in normal volunteers with emphasis on their relationship to sleep and their reversal by two specific benzodiazepine receptor antagonists (Ro 15-1788 and Ro 15-3505). The test battery was based on available clinical tests to assess various aspects of encoding and recall. The results suggest that flunitrazepam impairs acquisition of new information by interfering with encoding, and that these effects are clearly independent of sleep. Flunitrazepam effects on memory were fully reversed by both antagonists, as were the subjective and objective signs of sedation. This speaks against the hypothesis of different receptors for sedative and amnestic effects. Ro 15-3505 had shorter lasting effects than Ro 15-1788 and interfered with some tests; this is discussed in relation to its inverse agonistic effects.
Gentil
V
V
Departamento de Psiquiatria, Faculdade de Medicina, Universidade de Sao Paulo, Brazil.
Gorenstein
C
C
Camargo
C H
CH
Singer
J M
JM
D000328:Adult; D001570:Benzodiazepinones / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D005442:Flumazenil / Q000494:pharmacology*; D005445:Flunitrazepam / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D008297:Male; D008568:Memory / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects*; D011581:Psychological Tests; D012153:Retention, Psychology / Q000187:drug effects; D012691:Serial Learning / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects; D014706:Verbal Learning / Q000187:drug effects
D001570:Benzodiazepinones; D005442:Flumazenil; D005445:Flunitrazepam; C040725:Ro 15-3505