Preferential affinity of 3H-2-oxo-quazepam for type I benzodiazepine recognition sites in the human brain

Life Sci. 1988;42(2):189-97. doi: 10.1016/0024-3205(88)90682-0.


The hypnotic drug quazepam and its active metabolite 2-oxo-quazepam (2-oxo-quaz) are two benzodiazepines (BZ) containing a trifluoroethyl moiety on the ring nitrogen at position 1, characterized by their preferential affinity for Type I BZ recognition sites. In the present study we characterized the binding of 3H-2-oxo-quaz in discrete areas of the human brain. Saturation analysis demonstrated specific and saturable binding of 3H-2-oxo-quaz to membrane preparations from human cerebellum. Hill plot analysis of displacement curves of 3H-flunitrazepam (3H-FNT) binding by 2-oxo-quaz yielded Hill coefficients of approximately 1 in the cerebellum and significantly less than 1 in the cerebral cortex, hippocampus, caudate nucleus, thalamus and pons. Self and cross displacement curves for 3H-FNT and 3H-2-oxo-quaz binding in these brain areas indicated that 2-oxo-quaz binds with different affinities to two populations of binding sites. High affinity binding sites were more abundant in the cerebellum (95% of total sites), cerebral cortex, hippocampus and thalamus, whereas low affinity sites were predominant in the caudate nucleus and pons. Competition studies of 3H-2-oxo-quaz (2 nM) and 3H-FNT (0.5 nM) using unlabelled ligands indicated that compounds which preferentially bind to Type I sites are more potent at displacing 3H-2-oxo-quaz than 3H-FNT from cerebral cortex membrane preparations. The results suggest that 3H-2-oxo-quaz may be used for selectively studying Type I BZ recognition sites in the human brain.

MeSH terms

  • Adult
  • Anti-Anxiety Agents / metabolism*
  • Anti-Anxiety Agents / pharmacology
  • Benzodiazepines*
  • Benzodiazepinones / metabolism*
  • Binding, Competitive
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Female
  • Flunitrazepam / metabolism
  • Flunitrazepam / pharmacology
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Organ Specificity
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*


  • Anti-Anxiety Agents
  • Benzodiazepinones
  • Receptors, GABA-A
  • Benzodiazepines
  • Flunitrazepam
  • 2-oxoquazepam