Selective antagonists of benzodiazepines

  title={Selective antagonists of benzodiazepines},
  author={Walter Hunkeler and Hanns Möhler and Lorenzo Pieri and Petar Polc and Erico P. Bonetti and R. Cumin and Rudolf Schaffner and Willy E. Haefely},
Benzodiazepines produce most, if not all, of their numerous effects on the central nervous system (CNS) primarily by increasing the function of those chemical synapses that use γ-amino butyric acid (GABA) as transmitter1,2. This specific enhancing effect on GABAergic synaptic inhibition is initiated by the interaction of benzodiazepines with membrane proteins of certain central neurones, to which drugs of this chemical class bind with high affinity and specificity3,4. The molecular processes… 
A physiological role of the benzodiazepine/GABA receptor-chloride ionophore complex in stress.
This chapter will briefly summarize the evidence implicating the benzodiazepine receptor complex in the response to stress and anxiety, and present some recent findings from the laboratory which supports this hypothesis.
Pharmacological profiles in vivo of benzodiazepine receptor ligands
A recent increase in the number of benzodiazepine receptor ligands with in vivo activities allows comparison of a range of compounds from several different structral groups and their pharmacological profiles suggest that these compounds all fit onto a continuum of behavioural effects related to activation of benzdiazepine receptors.
Interactions of carbamazepine with benzodiazepine receptors
It is demonstrated that this anticonvulsant, at therapeutic concentrations, may bind to adenosine receptors in the brain, while not directly influencing the binding of radioligands to several neurotransmitter (GABA, glutamate, muscarinic cholinergic or P-adrenergic) receptors (Skerritt et al 1982~).
Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology
The isolation of a cloned cDNA encoding a new GABAA receptor subunit, termed γ2, which shares approximately 40% sequence identity with α-and β-subunits and whose messenger RNA is prominently localized in neuronal subpopulations throughout the CNS.
Molecular structure of benzodiazepine receptors
  • J. Tallman
  • Biology, Chemistry
    Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 1985
Benzodiazepines in perspective (II): The GABAA-Benzodiazepine Receptor Ligands
The benzodiazepine receptor (BDZ-R) is the most intensively studied allosteric site, and the GABAA-R system shows a high plasticity, which raises the possibility that ligands selective for distinct subtypes of BDz-R may emerge as useful drugs.
Hepatic Encephalopathy and Benzodiazepine Receptor Ligands
Benzodiazepine (BZ) receptor ligands interact with specific binding sites on the GABAA receptor/chloride channel complex on neurons in the central nervous system (CNS) (1) (Figure 1). Such ligands
Pharmacodynamic approaches to benzodiazepine action in man.
It would be useful to develop techniques to measure benzodiazepine receptor sensitivity in vivo, in order to determine whether psychiatric disorders such as depression or anxiety may be characterized by alterations in Benzodiazepines receptor sensitivity.


An endogenous protein modulates the affinity of GABA and benzodiazepine receptors in rat brain
This work has reported the presence of a high affinity, saturable, stereospecific binding site for benzodiazepines in synaptic membrane preparations obtained from brain of different animal species, including man, and this high affinity binding is now used to determine the therapeutic potency and to study the mode of action of Benzodiazepine in anxiety.
Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding.
  • C. Braestrup, R. Squires
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1977
Specific [3H]diazepam binding to membranes appears to be restricted to brain, where it is unevenly distributed: the density of diazepam receptors is about five times higher in cortex (the highest density) than in pons-meddula (lowest density).
Benzodiazepine receptor: demonstration in the central nervous system
Competition for the receptor by various benzodiazepines closely parallels their pharmacological potency, and binding to the receptor is stereospecific.
The use of naloxone in the treatment of diazepam poisoning.
  • E. Bell
  • Medicine
    The Journal of pediatrics
  • 1975
Physostigmine reversal of diazepam.