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Core structures of selected nonbenzodiazepines (left three diagrams) and the structure of benzodiazepine (right) for comparison.

The nonbenzodiazepines are comparatively new drugs whose actions are very similar to those of the benzodiazepines, but are structurally unrelated to the benzodiazepines and are believed to have fewer side effects. Thus far three main structural classes of nonbenzodiazepine drugs have been developed (although note that some other orphan drugs also fall into the nonbenzodiazepine category). The three main groups are:

  • Cyclopyrrolones

The first three nonbenzodiazepine drugs to enter the market were the "Z-drugs", zopiclone, zolpidem and zaleplon. These three drugs are all strong sedatives used exclusively for the treatment of insomnia. They have proved to be much safer than traditional sedatives such as benzodiazepines and barbiturates, especially when taken in overdose, and also have less of a tendency to induce dependence and addiction (although these issues can still become a problem with extended use). These advantages have led to the Z-drugs becoming widely prescribed for the treatment of insomnia particularly in elderly patients, in preference to older sedatives.[1][2][3]

However the Z-drugs are not without their disadvantages, and all three compounds are notable for producing side effects such as pronounced amnesia and more rarely hallucinations,[4][5] especially when used in large doses. More rarely these drugs can produce a fugue state where the patient sleepwalks and may perform relatively complex actions, including cooking meals or driving cars, while effectively unconscious and with no recollection of the events upon awakening. While this effect is rare (and has also been reported to occur with some of the older sedative drugs such as temazepam and secobarbital) it can be potentially hazardous and so further development of this class of drugs has continued in an effort to find new compounds with further improved profiles.[6][7][8][9][10]

More recently, a range of non-sedating anxiolytic drugs derived from the same structural families as the Z-drugs have been developed, such as alpidem and pagoclone, and are starting to be marketed. These drugs are again much more selective than the older benzodiazepine anxiolytics, producing effective relief of anxiety symptoms but with little or no sedative or amnestic side effects, and so offer considerable advantages over the older anxiolytic drugs, however they are still new to the market and have not yet been widely prescribed.


  1. Neubauer DN (2006). New approaches in managing chronic insomnia. CNS Spectrums 11 (8 Suppl 8): 1–13.
  2. Najib J (2006). Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment of transient and chronic insomnia. Clinical Therapeutics 28 (4): 491–516.
  3. Lieberman JA (2007). Update on the safety considerations in the management of insomnia with hypnotics: incorporating modified-release formulations into primary care. Primary Care Companion to the Journal of Clinical Psychiatry 9 (1): 25–31.
  4. Stone JR, Zorick TS, Tsuang J (2007). Dose-related illusions and hallucinations with zaleplon. Clin Toxicol (Philadelphia): 1–2.
  5. Toner LC, Tsambiras BM, Catalano G, Catalano MC, Cooper DS (2000). Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol 23 (1): 54–8.
  6. Mellingsaeter TC, Bramness JG, Slørdal L (2006). [Are z-hypnotics better and safer sleeping pills than benzodiazepines?]. Tidsskrift for den Norske Laegeforening 126 (22): 2954–6.
  7. Yang W, Dollear M, Muthukrishnan SR (2005). One rare side effect of zolpidem--sleepwalking: a case report. Archives of Physical Medicine and Rehabilitation 86 (6): 1265–6.
  8. Lange CL (2005). Medication-associated somnambulism. Journal of the American Academy of Child and Adolescent Psychiatry 44 (3): 211–2.
  9. Morgenthaler TI, Silber MH (2002). Amnestic sleep-related eating disorder associated with zolpidem. Sleep Medicine 3 (4): 323–7.
  10. Liskow B, Pikalov A (2004). Zaleplon overdose associated with sleepwalking and complex behavior. Journal of the American Academy of Child and Adolescent Psychiatry 43 (8): 927–8.

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