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induced sedation

Hydroxyzine (Atarax, Vistaril)

Anxiety

Lorazepam (Ativan)

Anxiety

Midazolam (Versed)

Anesthesia

Oxazepam (Serax)

Anxiety

Prazepam (Centrax)

Anxiety

Propranolol (Inderal)

Anxiety

Temazepam (Restoril)

Insomnia

Triazolam (Halcion)

Insomnia

Zolpidem (Ambien)

Insomnia

Zaleplon (Sonata)

Insomnia

acid (GABA), which is the major inhibitory neurotransmitter in the mammalian brain. Benzodiazepines potentiate GABAergic neurotransmission in essentially all areas of the central nervous system. This enhancement is thought to occur indirectly at the postsynaptic GABAa receptor complex.

The functional significance of this drug-receptor interaction is that the receptor complex regulates the entrance of chloride into the postsynaptic cells. The increase in chloride conductance mediated by GABA is intensified by the benzodiazepines. This facilitation of GABA-induced chloride conductance results in greater hyperpolarization of these cells and therefore leads to diminished synaptic transmission.

Another chemical class of sedative-hypnotic drugs, the barbiturates, also binds to receptors associated with the GABA-chloride ionophore, but these drugs appear to prolong rather than intensify GABA's effects. Fig. 24.4 shows the presumed drug receptor-GABA-chloride ionophore relationship.

In addition to the clinically useful benzodiazepines, which act as agonists at the benzodiazepine receptor, at least two other types of ligands also interact with this binding site. These are the benzodiazepine receptor antagonists and the inverse agonists. For example, flumazenil (Romazicon) is a receptor antagonist that selectively blocks the effects of other benzodiazepines at their binding sites; it has clinical application in the treat ment of benzodiazepine overdose and in the reversal of benzodiazepine-induced sedation. The inverse agonists are compounds that interact with benzodiazepine receptors and decrease, rather than increase, GABA-mediated changes. They also can antagonize the effects of benzodiazepine agonists and when administered alone, can be anxiogenic and proconvulsant.

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