A radioreceptor assay to study the affinity of benzodiazepines and their receptor binding activity in human plasma including their active metabolites.
1 A radioreceptor assay has been established to measure the receptor affinities of numerous benzodiazepines in clinical use. 2 The time course of receptor binding activity was studied by this method in the plasma of eight healthy subjects randomly treated with 1 mg lormetazepam (Noctamid, 2 mg flunitrazepam (Rohypnol, and 10 mg diazepam (Valium, and placebo on a cross-over basis. Blood samples were collected up to 154 h after treatment. 3 Receptor affinities of numerous benzodiazepines on vitro show good correlation with therapeutic human doses (r = 0.96) and may be predictive of drug potency in man. 4 Mean peak plasma levels of lormetazepam binding equivalents were 4.8 +/- 1 ng/ml at 2 h after lormetazepam, 7.2 +/- 1.8 ng/ml at 8 h after flunitrazepam, and 17.9 +/- 2.7 ng/ml at 15 h after diazepam. Plasma elimination half-lives of benzodiazepine binding equivalents were 9.3, 23 and 63 h, respectively. 5 Slow elimination of benzodiazepine binding equivalents following flunitrazepam and diazepam may be due to persistent active metabolites.
D000328:Adult; D014151:Anti-Anxiety Agents / Q000097:blood*; D001569:Benzodiazepines; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D003975:Diazepam / Q000097:blood; D005260:Female; D006801:Humans; D008140:Lorazepam / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D009567:Nitrazepam / Q000097:blood; D003708:Nordazepam / Q000097:blood; D011485:Protein Binding; D011869:Radioligand Assay; D011955:Receptors, Drug / Q000378:metabolism*; D011963:Receptors, GABA-A
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D003708:Nordazepam; D009567:Nitrazepam; C023842:lormetazepam; D008140:Lorazepam; D003975:Diazepam