[Pharmacoclinical competition between the benzodiazepines. Demonstration with diazepam and flunitrazepam in man].
While using a new benzodiazepines flunitrazepam by the intravenous route in ordinary anethesia a competitive action with another benzodiazepine which is being used for the last 15 years, namely diazepam, was demonstrated for the first time in man. This study on 170 patients operated for ear, nose and throat conditions demonstrated this phenomenon, confirmed it and it was possible to reproduce the effect. The interaction is mainly characterized by: - A reduction of the effects of flunitrazepam (less profound sleep, even wakefulness with a waking patient who could talk and could react to pain). This effect was obtained with injection of a normal clinical dose of diazepam. - There was a blocking action or a reduction in the pharmacological action normally expected of flunitrazepam by the previous administration of a clinical dose of diazepam, when given by the intravenous, intramuscular or oral routes. This suggests that there are common receptor sites for these two benzodiazepines at the cerebral level and this would explain this apparently paradoxical action. Even though flunitrazepam has a greater affinity for these receptor sites this molecule seems to be displaced, according to the law of mass action, by diazepam when used at a high dose. This interaction shown for these two benzodiazepines is also seen in other derivatives of the same chemicals series. This is important in therapeutics with the increasing use of these products in general medicine, and anesthetics and neuropsychiatry where they are quite often used in association.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000771:Anesthesia, Intravenous; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors*; D001667:Binding, Competitive; D002648:Child; D002675:Child, Preschool; D003975:Diazepam / Q000378:metabolism / Q000494:pharmacology*; D005445:Flunitrazepam / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008875:Middle Aged
D014151:Anti-Anxiety Agents; D005445:Flunitrazepam; D003975:Diazepam
Compétition pharmacoclinique entre les benzodiazépines. Mise en évidence chez l'homme avec le diazépam et le flunitrazépam.