Benzodiazepine sedative-hypnotics receptor interactions

Buspirone has selective anxiolytic effects, and its pharmacologic characteristics are different from those of other drugs described in this chapter. Buspirone relieves anxiety without causing marked sedative, hypnotic, or euphoric effects. Unlike benzodiazepines, the drug has no anticonvulsant or muscle relaxant properties. Buspirone does not interact directly with GABAergic systems. It may exert its anxiolytic effects by acting as a partial agonist at brain 5-HTia receptors, but it also has affinity for brain dopamine D2 receptors. Buspirone-treated patients show no... 

An acute action of melatonin of much interest is a sedative activity not mediated by an interaction with benzodiazepine or cannabinoid receptors. There is hope of developing a new type of hypnotic agent from this approach. A rather different aspect, potentially of great importance, is the use of melatonin analogues for re-establishing the circadian sleep rhythm when this is disturbed e.g. jet-lag, in the elderly and in disease (e.g. Alzheimer s disease). 

Compound 24 is a gamma-aminobutyric acid (GABA) receptor modulator that interacts with the GABA-A sub-type which is, in turn, the same locale where the classical benzodiazepine anxiolytics are also thought to interact (diazepam or Valium being a common benzodiazepine structure shown above as 57). Although 24 is classed as a nonbenzodiazepine sedative-hypnotic because it has... 

Using molecular biological techniques, point mutations of the a subunits have revealed that the sedative effects of the benzodiazepines likely result from an Interaction with the ai subunit, whereas the anxiolytic effects result from an interaction at the 02 subunit (27,28), as shown in Figure 15.10 and Table 15.3. Nonbenzodiazepine receptor agonists, such as the sedative-hypnotics indiplon, zaleplon, zolpicone, and zolpidem (see Chapter 19), are ai subunit-preferring ligands, as shown in Table 15.3 (29). 

It belongs to azapirones which is chemically and pharmacologically distinct class. It acts as a partial agonist at serotonin and dopamine receptors and having no hypnotic and sedative action. It does not interact with benzodiazepine receptor or modify GABA-ergic transmission. 

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