Z drugs: discover how they work

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What are Z drugs? How do they differ from other hypnotics? What side effects do they have? We’ll tell you in this article!
Z-drugs are a class of medications that differ from other hypnotic agents in their duration of action and side effects. There are 3 Z-drugs: zolpidem, zoplicone, and zaleplon . There are many medications for the treatment of insomnia, but Z-drugs cause little or no alteration in sleep architecture.

Insomnia has numerous causes and can be implicated in the onset, worsening or relapse of many psychiatric disorders. However, it can also be a symptom that something is not right. Sleep is a basic human need and studies recommend that, for adults, it is advisable to sleep between 7 and 9 hours a day.

What do we talk about when we refer to dream architecture?

Sleep is a physiological process regulated by hormones switching on and off with each other. It is a large electrical and chemical circuit . When we talk about sleep architecture, we are referring to the phases that the brain goes through from when we are awake until we are deeply asleep:

  • Phase I or drowsiness: sleep occurs very lightly, our muscles begin to relax and our eyes move slowly.
  • Phase II  or light sleep: heart rate and breathing rate decrease, as does temperature, and our eyes barely move.
  • Phase III  or transition: This is the phase in which our brain prepares for deep sleep. Our muscles are relaxed and a type of waves characteristic of deep sleep appear: delta waves.
  • Stage IV or deep sleep: both breathing and heart rate are slowed. Delta waves predominate. This is the restorative phase of sleep.
  • Phase V or REM phase: it is called this because it is the phase in which we typically dream. When we dream, our eyes move as if we were actually seeing what we are dreaming about while awake.

Sleep is a cyclical process . Our brain takes approximately 90 minutes to start phase I and finish phase V. These phases are repeated throughout the 8 hours we usually sleep. So, on average, we go through each of these phases about 5 times a night .

An approach to the neurobiology of sleep

We are awake (vigilant) or asleep depending on the stimuli we receive and the degree of activation we have. In our brains there are molecules called neurotransmitters that are responsible for regulating the mechanisms that make us awake. They are the molecules that control how much and how activated we are.

What is a neurotransmitter and a receptor?

A neurotransmitter is a key . Two key neurotransmitters regulate the sleep-wake switches: histamine and GABA .

  • Histamine : This is one of the neurotransmitters that regulate wakefulness. When there is a lot of histamine, we are awake . But when there is little, we feel sleepy. That is why the antihistamines that we can take for the flu cause sleepiness. Because they reduce (anti) the amount of histamine in the areas of the brain that are responsible for sleep.
  • GABA:  acts in the opposite way to histamine. It is the main neurotransmitter responsible for making us fall asleep . We can say that GABA is an inhibitory neurotransmitter because it “turns off” the brain regions that are responsible for keeping us awake.
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In a pedagogical sense, we can think of brain function as an electrical system full of circuits. In neurobiology, the circuits that control sleep and wakefulness are called the ascending reticular activating system .  This system contains on and off switches. The ones that are relevant to the topic we are discussing here are:

  • The off switch : This is the brain region responsible for making us fall asleep, the sleep promoter. It is located in a region called the ventrolateral preoptic nuclei (VLPGN) , in the hypothalamus. When this region is activated, it produces the neurotransmitter GABA.
  • The  on/off switch : This is the region with the opposite function and when activated, it produces the neurotransmitter histamine and we wake up. It is located inside the tuberomammillary nuclei (TNM) of the hypothalamus.

These mechanisms act in a special way known as a flip-flop mechanism :  they cannot both be on or off at the same time. When one is on, the other must necessarily be off and vice versa.

In our brains we have multiple keys for multiple locks . The lock that interests us here, because of its relationship with Z Drugs, is called GABA-A. The GABA-A receptor or lock works very well for the GABA neurotransmitter or key. Thus, when GABA and GABA-A come together, like a key in its lock, they produce sleep.

The brain also responds to the amount of light in our environment. When we are in brightly lit places or it is daytime, the light causes a region of the brain to turn off. This area is known as the suprachiasmatic nucleus, and is located in the hypothalamus. When the light decreases, this area of ​​the brain is no longer off: the suprachiasmatic nucleus is activated and secretes a hormone that also induces drowsiness: melatonin .

Pharmacological treatment of insomnia

We can understand insomnia as a state of activation during the night, the product of an overactive brain . From a neurobiological perspective we can explain it as the activation of the on switch at night.

Drugs that reduce brain activation are those that, when we need to sleep but cannot, force the off switch to activate.  Since this mechanism is, remember, a flip-flop mechanism, the on switch will necessarily be deactivated. Hypnotic drugs include benzodiazepines, antihistamines and Z drugs.

Benzodiazepines

Benzodiazepine hypnotics  act as keys to the GABA-A lock: they cause sleep.  They are drugs that serve both to induce sleep (hypnotics) and to reduce anxiety (anxiolytics). Examples of benzodiazepines are lormetazepam, lorazepam, clonazepam, diazepam, or alprazolam.

What side effects do they present? Among others:

  • They can be addictive with continued use. Therefore, we recommend that you consult your specialist on how to take them.
  • They can cause hangover-like symptoms when we wake up.
  • When we stop taking them, they can cause an increase in insomnia: rebound insomnia.
  • They also interfere with long-term memory.
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Antihistamines

If we recall, histamine was the neurotransmitter that turned on the on switch. If we introduce a drug that reduces the amount of histamine, the on switch will no longer be active . And because the mechanism is a flip-flop, automatically the other switch, the off switch, will be turned on. This is what antihistamines do. Examples of antihistamine drugs are doxylamine or diphenhydramine.

What side effects do they present? Among others:

  • Sleepiness.
  • Dizziness and headaches.
  • Fatigue.
  • Dry mouth and constipation.
  • Blurred vision.
  • Vertigo.

Z drugs

The Z-drugs were synthesized during the early 1980s and have a sedative and hypnotic effect similar to that of the benzodiazepines. The Z-drugs zaleplon, zolpidem, and zoplicone also act as keys that bind to the GABA-A receptor or lock, but in a slightly different way than the benzodiazepines do.

These drugs bind to GABA-A in such a way that they do not produce as much tolerance (less effect after taking the drug for a long time) or dependence (rebound insomnia after abruptly stopping treatment). They have no known side effects on consciousness, memory and learning.

  • Zoplicone : is a drug with sedative, hypnotic, muscle relaxant and anticonvulsant effects. Although it has only been approved for use in the treatment of insomnia. The most frequently reported adverse effect is persistent bitter taste in the mouth (dysgeusia), dry mouth (xerostomia), difficulty waking up, drowsiness and headache. Its effect lasts between 4 and 5 hours.
  • Zolpidem : when administered in low doses, it does not produce dependence or tolerance. Among the effects of zolpidem we can find its sedative action, greater than its anxiolytic action, that is, it makes us sleepy rather than relaxing. It is indicated as a  short-term treatment for insomnia . One of its most particular adverse effects is hallucinations. Its effect lasts between 1.5 and 2.5 hours.
  • Zaleplon is a drug that is attributed with several actions. It is a sedative, hypnotic, muscle relaxant and anticonvulsant. It does not produce tolerance or amnesia, nor motor alterations the day after taking the drug. Of the three Z drugs, it is the one with the shortest effect: only 1 hour.

Because of their short duration, Z drugs are indicated for initial insomnia, that is, when we have trouble sleeping. They are not as effective drugs for maintenance insomnia (when we wake up many times during the night), or for mixed insomnia (when we have a lot of trouble sleeping and, in addition, we wake up many times during the night).

As clear as this article has been, remember that we are talking about a drug that directly affects the activity of our brain. Therefore, I recommend that you talk to your doctor before you start using it and follow his instructions.