Benzodiazepines

Abstract

Benzodiazepines are a group of drugs with wide application as tranquillizers, hypnotics, muscle relaxants and anticonvulsants. They act by enhancing γ‐aminobutyric acid (GABA)ergic synaptic inhibition in the brain.

Keywords: inhibitory neurotransmission; diazepam; tranquillizer; anxiolytic drug; insomnia; anxiety disorders; antiepileptic drugs

Figure 1.

Excitatory and inhibitory neurotransmission. Ligand‐gated ion channels, which are selectively permeable to particular cations or anions, mediate excitatory and inhibitory neurotransmission. The principal excitatory and inhibitory neurotransmitters are glutamate and γ‐aminobutyric acid (GABA), respectively.

Figure 2.

γ‐Aminobutyric acid (GABA)ergic synapse. After being released from the nerve terminal, the neurotransmitter GABA activates GABAA receptors located in the postsynaptic membrane. They constitute GABA‐gated chloride channels (Cl) whose performance is enhanced in the presence of a benzodiazepine (e.g. diazepam). The action of GABA is terminated by GABA transporters (GT), by which the neurotransmitter is taken up into the nerve terminal.

Figure 3.

Diazepam, the prototypical benzodiazepine drug. The chemical structure of diazepam, a 1,4‐benzodiazepine, and the pharmacological spectrum of benzodiazepine drugs. Therapeutic indications and chemical structures of various other benzodiazepine drugs are given in Table and Table , and in Figure .

Figure 4.

Chemical structures of benzodiazepine drugs.

Figure 5.

Enhancement of the γ‐aminobutyric acid (GABA) response by a benzodiazepine. In the presence of a benzodiazepine (e.g. diazepam), the dose–response curve of GABA is shifted to the left. The action of benzodiazepines is activity dependent and self‐limiting: in the absence of GABA, the benzodiazepine has no potentiating effect (bottom left part of the curves); when the GABA response is maximal, it is not further enhanced by the benzodiazepine (top right).

Figure 6.

Structure–activity relationship of the benzodiazepines. The pharmacological potency of benzodiazepines correlates closely with their affinity to the benzodiazepine‐binding site. This is exemplified for the muscle relaxant activity of various benzodiazepines. Their affinity was determined by competition for the binding site with [3H]diazepam. The numbers refer to benzodiazepines not in clinical use. Edmin, minimum effective dose.

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Further Reading

Collinson N (2002) Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the α5 subunit of the GABAA receptor. Journal of Neuroscience 22: 5572–5580.

Crestani F, Keist R and Fritschy JM (2002) Trace fear conditioning involves hippocampal α5 GABAA receptors. Proceedings of the National Academy of Sciences of the USA 99: 8980–8985.

Kupfer DJ and Reynolds CF (1997) Management of insomnia. New England Journal of Medicine 336: 341–346.

Löw K, Crestani F and Keist R (2000) Molecular and neuronal substrate for the selective attenuation of anxiety. Science 290: 131–134.

McKernan RM, Rosahl TW and Reynolds DS (2000) Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABAA receptor α1 subtype. Nature Neuroscience 3: 587–592.

Möhler H and Okada T (1977) Benzodiazepine receptor: demonstration in the central nervous system. Science 198: 849–851.

Möhler H, Benke D, Benson J et al. (1997) Diversity in structure, pharmacology and regulation of GABAA‐receptors. In: Enna SJ and Bowery NG (eds) The GABA Receptors pp. 11–36. Totowa, NJ: Humana Press.

Rudolph U, Crestani F, Benke D et al. (1999) Benzodiazepine actions mediated by specific GABAA‐receptor subtypes. Nature 401: 796–800.

Shader RJ and Greenblatt DJ (1993) Use of benzodiazepines in anxiety disorders. New England Journal of Medicine 328: 1398–1405.

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How to Cite close
Möhler, Hanns(Jan 2006) Benzodiazepines. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0004084]