New directions in the treatment of insomnia

Abstract

Sleep-related complaints are common in the general population. Prevalence rates are significantly higher among women and the older age groups. In addition, a substantial number of those experiencing insomnia state that the complaint is chronic. The management of chronic primary insomnia combines nonpharmacological measures and pharmacotherapy. In patients with chronic secondary insomnia, hypnotic medication may be beneficial as an adjunct to treatment of the primary disorder. Presently available hypnotic drugs include the benzodiazepines and the nonbenzodiazepine derivatives zopiclone, eszopiclone, zolpidem and zaleplon. The finding that the sedative/hypnotic effect of benzodiazepine and nonbenzodiazepine compounds is mediated through GABA_A receptors containing the α₁ subunit presents new possibilities for designing more effective and safe hypnotic drugs. Imidazopyridinone, imidazolyl-methyl-imidazole, ring-fused-imidazole, imidazolyl-methyl-pyridazine, imidazolyl-methyl-pyrimidine, imidazolyl-methyl-pyridine, imidazolyl-methyl-pyrazine, aryl acid pyrimidinyl-methyl-amide and pyridazinyl-methyl-amide, and pyrrolo-pyridine carboxylic acid amide derivatives have been reviewed that could be particularly useful in treating primary insomnia and secondary insomnia as an adjunct to treatment of the primary disorder. A range of tachykinin antagonists, including pyperidyl-carboxamide, C-aryl-piperidine, diazabicycle-piperidine, cyclic amine and N-benzyl-phenyl-heterocyclyl-propionamide derivatives, are being developed for insomnia treatment. However, there is little evidence to suggest that they will be a valid alternative for the management of insomnia.

Keywords::

• α₁ subunit
• benzodiazepine hypnotic
• eszopiclone
• GABA_A receptor agonist
• melatonin ligand
• primary insomnia
• secondary insomnia
• serotonin ligand
• sleep
• tachykinin antagonist
• wakefulness
• zaleplon
• zolpidem
• zopiclone