Sedative - Hypnotics: Zolpidem

Zolpidem is Ambien. It is considered a benzodiazepine by the FDA, class IV. Ambien is very, very unlikely to produce dependence, habituation, or tolerance.


There is a receptor in the CNS that recognizes GABA. When it binds to GABA it results in a chloride influx and thus has inhibitory effects on neuronal firing. Benzodiazepines act on a specific receptor for benzodiazepine, separate from the GABA receptor. When benzodiazepine binds its receptor, the same thing happens as when GABA binds its receptor; there is a net influx of chloride and a stabilizing effect because of the decrease in neuronal firing, resulting in drowsiness. Benzodiazepines also help in treating seizure disorders because of their stabilizing effects on neuronal transmission. There is cooperativity between GABA and benzodiazepine. Ambient works on ANOTHER analogous receptor (separate still from both the GABA and benzodiazepine receptors), called omega-1.



Ambien does not produce any other effects aside from normal sleep. Zolpidem (Ambien) has no significant effect on mean percentage of time in each stage of sleep, compared to normal. There is no significant effect on REM activity. Duration of sleep is increased in insomniacs. No evidence of developing tolerance (1 month dosing) and no evidence of rebound insomnia (more difficult to fall asleep after ceasing tx with Ambien). Ambient is classified as a schedule IV drug, meaning that although tolerance is a remote possibility, the drug is not absolutely free of the potential to cause tolerance.



Ambien is only approved for treatment of insomnia. Zolpidem adverse reactions don’t seem to be too significant as compared to a placebo. For headache and nausea, in short-term trials, Ambien shows no significant difference from a placebo. In long term trials, drowsiness is a little higher than the placebo, but very good as compared to other drugs. Amnesia occurs very rarely with Ambien, unlike with benzodiazepines (which can be used in dentistry to produce quality amnesia after a dental extraction, for example).



This is an ad for the Ambien derivative, Sonata. Prescriptions for sonata should not exceed a one month supply… this is different than Ambien, which is usually given 10-14 days.



Do these drugs really promote sleep onset? Zolpidem (Ambien) is very good compared to Halcion or some of the other long-acting benzodiazepines. This is the virtue that allowed ambient to become more popular. Flurazepam has an active metabolite, the elderly are prone to residual daytime drowsiness.



There is a hormone produced by the pineal gland, melatonin, which acts on a melatonin receptor in the Pons, and can induce sleep. As you age, melatonin production declines markedly, thus the elderly have a hard time sleeping. Pts can buy otc melatonin, usually combined with other vitamins. Melatonin can also be used by pts who anticipate jet-lag; it is not considered a drug.

Category: Pharmacology Notes