Imidazopyridine hypnotics

Zolpidem (an imidazopyridine) and zopiclone (a cyclopyrrolone) are hypnotics that, despite their different chemical structure, possess agonist activity at the benzodiazepine receptor (p. 226). 

Zolpidem is an imidazopyridine, with a chemical structure of N,N,6-trimethyl-2-(4-methylphenyl)-imidazo [ 1,2-alpha] -pyridine-3-acetamine hemitartrate (Salva and Costa, 1995). This nonbenzodiazepine sedative hypnotic was first released in Europe, and then introduced in the United States in 1993 (Hobbs et ah, 1996). Zolpidem has a strong sedative effect that seems to preclude its use as an anxiolytic. It has only weak anticonvulsant effects (Salva and Costa, 1995 Hobbs et ah, 1996). 

Zolpidem is a non-benzodiazepine hypnotic of the imidazopyridine class. It is a GABA receptor agonist selective for omega-1 receptor subunit. 

Several drugs with novel chemical structures have been introduced more recently for use in sleep disorders. Zolpidem, an imidazopyridine, zaleplon, a pyrazolopyrimidine, and eszopiclone, a cyclopyrrolone (Figure 22-4), although structurally unrelated to benzodiazepines, share a similar mechanism of action, as described below. Eszopiclone is the (S) enantiomer of zopiclone, a hypnotic drug that has been available outside the United States since 1989. Ramelteon, a melatonin receptor agonist, is a new hypnotic drug (see Ramelteon). Buspirone is a slow-onset anxiolytic agent whose actions are quite different from those of conventional sedative-hypnotics (see Buspirone). 

The newer sedative-hypnotics that are not benzodiazepines are rapidly becoming the first-line treatment for insomnia. These agents not only have pharmacodynamic advantages over benzodiazepines in terms of their mechanism of action, but perhaps more importantly, pharmacokinetic advantages as well. Three nonbenzodiazepine sedative-hypnotic agents that are now available are zaleplon (a pyrazolopyrimidine), zopiclone (a cyclopyrrolone not available in the United States), and zolpidem (an imidazopyridine) (Figs. 8—28-8—30 Table 8—4). 

Nicholson AN, Pascoe PA (1986) Hypnotic activity of an imidazopyridine (zolpidem). Brit J Clin Pharmacol 21 205-211... 

Zolpidem (an imidazopyridine), zale-plone (a pyrazolopyrimidine) and zopi-clone (a cyclopyrrolone) are hypnotics that, despite their different chemical structure, can bind to the benzodiazepine site on the GABAa receptor (p. 222). However, their effects do not appear to be identical to those of benzodiazepines. Thus, compared with benzodiazepines, zolpidem exerts a weaker effect on sleep phases, supposedly carries a lower risk of dependence, and appears to have less anxiolytic activity. Heterogeneity of GABAa receptors may explain these differences in activity. GABAa receptors consist of five subunits that exist in several subtypes. 

A number of compounds that have. structural characteristics broadly related to the benzodiazepines, including neuro-active flavanoids, imidazopyridines. and pyrazolopyriniid-iiKs. can act as positive mc ulators at the benzodiazepine recognition site on one or more of the GABAa receptor mbtypes. Compounds may produce all the characteristic actions of benzodiazepines or be selective, as are. for example, anxiolytic flavanoids or the. sedative-hypnotics zolpidem and zalephun. 

Zolpidem [ban, inn] (zolpidem tartrate [usanJ Ambien Stilnoct and many other names) is one of the imidazopyridines, and a non-benzodiazepine BENZODIAZEPINE BINDING-SITE AGONIST. Most of its properties are similar to diazepam, but with less ANTICONVULSANT, SEDATIVE and SKELETAL MUSCLE RELAXANT properties. It has HYPNOTIC activity and has been used to treat insomnia, zolpidem tartrate zolpidem. 

Lead optimization of imidazopyridines displaying optimal hypnotic properties led to the selection of SL 80, 0750 (zolpidem). 

Zolpidem is of the imidazopyridine class, and is used as a hypnotic agent. It is not considered a benzodiazepine. 

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