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Zopiclone is a very innovative and effective medication that is usually recommended for sleep-related issues. It belongs to the category of medicines called sedative-hypnotics.

Zopiclone is a great option for sleep pills, since it helps to prevent early morning awakenings, frequent wakeups during the night and it also effectively combats regular difficulties with falling asleep. However, as it is usually the case with sedative-hypnotics, it should be only taken by people whose troubles sleeping affect their regular functioning during the day, and it should not be taken for more than seven to ten consecutive days.

Zopiclone is a medicine that is available under several different brand names and presentations. Since particular brands may not carry all the presentations or effectively treat all the problems mentioned above, and particular presentations may not be recommended for every problem we have mentioned in here, you should always consult your physician before deciding which brand and presentation is the best option for your particular condition.

Imovan (Zopiclone)

Pharmacological group: hypnotics; non-benzodiazepines (Z-preparations)
Systematic (IUPAC) name: (RS) -6- (5-chloropyridin-2-yl) -7-oxo-6,7-dihydro-5H-pyrrolo [3,4-b] pyrazin-5-yl-4- methylpiperazine-1-carboxylate
Trade names: Imovane, Zimovane
Legal status: available only on prescription (Australia, United Kingdom, USA)
Uses: oral tablets, 3.75 mg (UK), 5 or 7.5 mg
Bioavailability: 52-59% binds to plasma proteins
Metabolism: various enzymes of liver cytochrome P450
Half-life: ~ 6 hours
Excretion: urine
Formula: C17H17ClN6O3
The pier. weight: 388.808 g / mol

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Zopiclone (trademark of Imovan in Canada, Australia, Sweden, Finland, Norway, Russia and the United Kingdom, the trademark Zimovane in Europe) is a nonbenzodiazepine hypnotic used in the treatment of insomnia. The substance is cyclopirrolone, which increases the normal transmission of the GABA neurotransmitter in the central nervous system, as well as benzodiazepines, however in a different way. Zopiclone is a sedative and is sold as a hypnotic. Its action is based on the calming or oppression of the central nervous system. After prolonged use of zopiclone, tolerance and habituation to the drug may occur. If the dose is lowered or the drug is stopped, an abstinence syndrome may develop, which may include a number of symptoms similar to those observed when benzodiazepines are withdrawn. In the United States, zopiclone is not a commercially available drug, however its active stereoisomer, Eszopiclone, is sold under the trademark Lunesta. Zopiclone is under the control of regulators in countries such as the United States, Japan, Brazil and some European countries. In these countries, possession of a drug without a prescription can be illegal. Zopiclone is also called the "Z-drug". Other Z-drugs include Zaleplon (Sonata) and Zolpidem (Ambien and AmbienCR). It is believed that such drugs less contribute to the development of habituation than benzodiazepines. However, in recent years, there have been more frequent reports of addiction and addiction to Z-medications. Zopiclone is recommended for taking on a short-term basis, usually within a week or less. Daily or continuous use of the drug is usually not recommended.

Medical use

Zopiclone is used for short-term treatment of insomnia, in which severe symptoms are problems with the onset of sleep or the maintenance of sleep. Long-term use of Zopiclone is not recommended, as long-term use of the drug may develop tolerance and dependence.

Elderly patients

Zopiclone, like other benzodiazepines and nonbenzodiazepines, causes irregularities in body balance and stability in standing position in patients with nocturnal awakenings or the next morning. Often reports of falls and fractures of the hip. The combination with alcohol increases the risk of such violations. In relation to such side effects, partial, but incomplete, tolerance can develop. An extensive review of the medical literature on the treatment of insomnia in the elderly has shown that there is sufficient evidence of the efficacy and long-term benefits of non-drug treatment for insomnia. Compared with benzodiazepines, nonbenzodiazepine hypnotics and sedatives, such as zopiclone, offer little benefit in efficacy or tolerability in the elderly. It has been found that new agents, such as melatonin agonists, may be more appropriate and effective for treating chronic insomnia in the elderly. There is still no sufficient evidence base for the safety of prolonged use of sedative hypnotics for insomnia. Such use is not recommended for reasons that include fears of possible adverse effects of drugs, including cognitive impairment (anterograde amnesia), day sedation, impaired coordination of motion and an increased risk of accidents and falls. In addition, the effectiveness and safety of long-term use of nonbenzodiazepine hypnotics is still to be determined. In order to assess the long-term effects of treatment and find the most appropriate treatment strategy for elderly people with chronic insomnia, further research is needed.

Adverse Reactions

Side effects, most commonly observed in clinical trials, were changes in taste sensations or dysgeusia (a bitter, metallic taste in the mouth that quickly disappears in most users, but some may persist until the half-life of the drug has elapsed). After stopping the drug, palpitations may occur during the day, especially after long periods of use. Zopiclone, like Triazolam and Rohypnol, causes memory disorders such as amnesia. The most significant side effect is a violation of driving skills and an increased risk of road accidents. This side effect is not unique to Zopiclone, but is also observed when other hypnotics are taken. A study evaluating the effect of zopiclone on driving skills the next day showed that the harmful effects of the drug on driving skills are two times stronger than the effects of alcohol. Zaleplon does not have a detrimental effect on driving skills the day after the application. Daytime anxiety associated with discontinuation of non-benzodiazepines, such as Zopiclone.

Frequent side effects

Gastrointestinal: taste disorders, including metallic taste and dry mouth. Nervous system: disorders of REM sleep, double vision, drowsiness, memory impairment, visual-spatial disorders, dizziness, headaches and fatigue. Also, unexpected mood changes are possible, in the event of which it should immediately stop taking the drug.

More rare side effects

Gastrointestinal: heartburn, constipation, diarrhea, nausea, and plaque on the tongue, bad breath, anorexia or increased appetite, vomiting, epigastric pain, indigestion, dehydration, paravgeziya.
Cardiovascular: palpitation in elderly patients.
Skin: urticaria, tingling in the hands and feet.
Miscellaneous: blurred vision, frequent urination, nocturnal enuresis, increased serum transaminase and / or alkaline phosphatase from mild to moderate, and interstitial nephritis (very rare).
Reproductive system: impotence, delay of ejaculation, anorgasmia in men and women.
Nervous system: agitation, anxiety, memory loss, including anterograde and retrograde amnesia, confusion, dizziness, weakness, drowsiness, fatigue, euphoria and / or dysphoria, a feeling of intoxication, depression, sleepwalking, coordination problems, hypotonia, speech disorder, hallucinations , as a rule, auditory and visual, behavioral disorders, aggression, tremor, relapse of insomnia, nightmares, hypomania. Delirium is mainly observed in the elderly.

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Tolerance, dependence and discontinuation

Zopiclone, a benzodiazepine-like preparation, was originally presented as a drug having a reduced risk of dependence and withdrawal symptoms compared to traditional benzodiazepine drugs. In fact, however, zopiclone may have even a slightly greater potential for dependence development than benzodiazepines. Tolerance to the effects of zopiclone may develop within a few weeks. In most cases, prolonged use of the drug should be avoided. The successful treatment of patients with severe insomnia as a result of anxiety can be carried out within a few months. A sharp discontinuation, especially with prolonged use of high doses of the drug, can cause convulsions and nonsense in severe cases. Publications in the British Medical Journal do not provide any evidence that zopiclone has a low potential for dependence development. In fact, when taking the drug often develops physical dependence, abuse and withdrawal symptoms, similar to those observed when benzodiazepines are abolished. Symptoms of withdrawal symptoms include anxiety, tachycardia, tremors, sweating, hot flashes, palpitations, derealization, and later - insomnia. There were also reports of seizures during withdrawal during the detoxification of Zopiclone, but in this case the person abused high doses of zopiclone. The risk of dependence when taking zopiclonaa for less than 2 weeks or less is very low. However, this is disputed in one study of low doses of zopiclone taken for 7 nights. It was found that stopping the use of zopiclone causes a relapse of insomnia. In addition, with the discontinuation of midazolam after continuous use for 7 nights, no relapse of insomnia was observed, suggesting that zopiclone may cause more significant problems of tolerance and dependence than benzodiazepines. After 3 weeks of use, with the discontinuation of zopiclone, there are symptoms of relapse from mild to moderate degree. Due to the risk of developing tolerance and physical dependence, zopiclone is recommended to be used for a short period of time (maximum 1-4 weeks), or, on the contrary, it is rare to use the drug for long periods of time. Long-term users of Zopiclone who have acquired physical dependence on the drug should not abruptly stop taking the substance, as severe withdrawal symptoms such as delirium may be associated with this. If zopiclone is taken for several weeks or more, stop taking the drug should be done by gradually reducing the dose or switching to an equivalent dose of diazepam (Valium), which has a much longer half-life, which facilitates withdrawal, and then gradually, for several months, reduce dosage to avoid the development of extremely severe and unpleasant withdrawal symptoms (such as internal anxiety, psychomotor agitation, abdominal pain, hypertension, hallucinations, seizures, anxiety and, depression, psychosis, etc.) which may last for up to two years at too abrupt discontinuation of treatment. After 4 weeks of zopiclone use at night, some users develop daily anxiety associated with discontinuation of the drug. This symptom, however, does not show as intensively as when taking triazolam, which has a much shorter period of action and causes more powerful symptoms of daytime anxiety associated with discontinuation, in long-term users. According to the World Health Organization, Zopiclone, although not molecularly benzodiazepine, is capable of binding to the same benzodiazepine binding site as benzodiazepines in a highly selective and high affinity. The World Health Organization also stated that zopiclone has cross-tolerance with benzodiazepines, and these drugs can replace each other. In a review of the zopiclone of the World Health Organization, it was found that the occurrence of withdrawal symptoms is usually observed either with excessive use of the drug or with prolonged use of zopiclone. Symptoms of zopiclone withdrawal include anxiety, tachycardia, tremor, sweating, relapse of insomnia, derealization, seizures, palpitations and hot flashes. Zopiclone has cross-tolerance with benzodiazepines. Alcohol has cross-tolerance with positive GABA receptor modulators, such as benzodiazepines and nonbenzodiazepines. For this reason, alcoholics or convalescent alcoholics may be at increased risk of physical dependence on zopiclone. In addition, alcoholics and drug addicts may be at increased risk of abuse and / or development of psychological dependence on zopiclone. Patients who suffer from alcoholism, drug abuse or who are physically or psychologically dependent on sedatives should avoid taking Zopiclone. Discontinuation of Zopiclone is recommended through switching to an equivalent dose of diazepam, since diazepam is available in low dosages, has cross-tolerance to zopiclone and lasts longer than zopiclone, which allows a smoother conclusion and allows the body to adjust to a constant dose. Although Zopiclone acts on the same benzodiazepine receptors that preparations of the benzodiazepine family, it is not classified as benzodiazepine (although it has a number of common characteristics and effects) due to differences in molecular structure. Zopiclone is classified as a cyclopyrrolone derivative.


A recent analysis of US FDA data and clinical trial results shows that non-benzodiazepine Z-preparations in prescribed doses cause an increased risk of developing cancer in humans. There were 15 epidemiological studies that showed that hypnotic drugs increase the risk of death, mainly due to increased deaths from cancer (brain, lungs, intestines, breast and bladder). One possible explanation for the increase in cancer mortality is that Z-drugs have a negative effect on the immune system. The fact that in clinical trials in patients taking other Z-drugs (zolpidem, zaleplon and eszaleplon) there was an increased level of diseases, can support this theory. Benzodiazepine hypnotics are also associated with an increased risk of ovarian cancer. The development of a malignant tumor was associated with the use of zolpidem, but so far nothing can be said about the relationship of zolpidem with the development of neoplasms. Indiplon, another non-benzodiazepine drug, also demonstrated an increased risk of developing cancer in clinical trials. The review concluded: "The likelihood of developing cancer is large enough, and doctors and patients should be aware that sleeping pills can increase the risk of cancer in patients."


Zopiclone causes a decrease in driving habits, like benzodiazepines. Long-term users of hypnotics develop only partial resistance to adverse effects of drugs associated with negative effects on driving skills. Users who take sleeping pills over the course of a year are still at risk of car accidents. When taking Zopiclone, you should refrain from driving a car. Zopiclone causes a worsening of the psychomotor function. The next day after taking Zopiclone, there may be an effect such as impairment of visual-motor coordination. Patients who have abused drugs in the past should avoid using Zopiclone because the substance has a very high potential for abuse. Zopiclone in some cases can cause a state of amnesia associated with sleepwalking, which can progress to the point where a person takes food, communicates with people (quite convincingly) and even drives a car, actually being in a dream. Therefore, the drug, as a rule, is not used as a sedative (like benzodiazepines), because patients during the action of the drug can make unprofitable decisions (because they are in a dream) and undertake dangerous activities, remembering nothing of the kind later.

Special Precautions

When using zopiclone, alcohol should be avoided, since alcohol and zopiclone increase the effect of each other, which may increase the risk of dependence. In patients with liver diseases zopiclone is excreted from the body much more slowly than in normal patients. Such patients experience more pronounced pharmacological effects of the drug. Zopiclone reduces resistance and increases the risk of falls in the elderly, and also has cognitive side effects. Falls are one of the most common causes of death in the elderly. Patients suffering from muscle weakness resulting from myasthenia gravis or with bad respiratory reserves due to a severe form of chronic bronchitis, emphysema, or other lung diseases, or experiencing sleep apnea should avoid using zopiclone. From the use of the drug should also refrain patients with untreated thyroid disease.

EEG and sleep

Like other sedative hypnotics, zopiclone causes a decrease in body temperature and is effective in reducing sleep latency. Zopiclone benzodiazepines causes similar changes in the EEG and Sleep Architecture and causes disturbances in the sleep architecture at the termination of the reception, as relapse effect. Zopiclone reduces delta waves and the number of high-amplitude delta waves, increasing the number of low-amplitude waves. Zopiclone reduces the total amount of time in the phase of fast sleep, and also delays its onset. Cognitive behavioral therapy is more effective in the treatment of insomnia than zopiclone, and has a long term impact on the quality of sleep for at least a year after treatment.


Zopiclone acts as a sleeping pill, anxiolytic, anticonvulsant and a muscle relaxant. Zopiclone and benzodiazepines randomly act on benzodiazepine-binding sites on a1, a2, a3 and a5 GABA-containing receptors as complete agonists, causing an increase in the effect of GABA, resulting in the observed therapeutic and adverse effects of zopiclone. The metabolite of zopiclone is called desmethylzopiclone. The substance is also pharmacologically active and exhibits predominantly anxiolytic properties. Like benzodiazepines, zopiclone and its active metabolite, desmethylzopiclone, also inhibit N-methyl-D-aspartate (NMDA) receptors and nicotinic acetylcholine receptors, which may affect the fact that these drugs are addictive. In one study, however, a small selectivity of zopiclone to a1 and a5 subunits was demonstrated. It is believed, however, that zopiclone binds indiscriminately to a1, a2, a3 and a5 receptor GABA benzodiazepine complexes. Desmethylzopiclone displays the properties of a partial agonist, in contrast to zopiclone, which is a complete agonist. The mechanism of action of zopiclone is close to the action of benzodiazepines, both substances have similar effects on motor activity and on the turnover of dopamine and serotonin. A meta-analysis of randomized controlled clinical trials comparing benzodiazepines and Zopiclone or other Z-drugs such as zolpidem and zaleplone showed that there are clear and consistent differences between zopiclone and benzodiazepines in terms of delay in onset of sleep, total sleep duration, quality of sleep, adverse effects, tolerance, recurrence of insomnia and daytime activity. Zopiclone is a member of the cyclopyrrolone family. Another drug of this class is Suriclone. Zopiclone, molecularly different from benzodiazepines, has an almost identical pharmacological profile, including anxiolytic properties. It acts through binding to the benzodiazepine site as a complete agonist, which in turn positively modulates the benzodiazepine-sensitive GABA receptors and enhances the binding of GABA to these GABA receptors, providing the pharmacological action of Zopiclone. In addition to its pharmacological properties, Zopiclone can act like barbiturates. In EEG studies, it has been shown that zopiclone significantly increases the energy of the beta-frequency group and shows the characteristics of high-voltage slow waves, the desynchronization of the theta of the hippocampus, and the increase in energy in the delta band. Zopiclone increases both the second phase of sleep and the phase of slow sleep, while zolpidem, the a1-selective compound, increases only the phase of slow sleep and has no effect on the second phase of sleep. Zopiclone less selectively affects the site of a1 and has a higher affinity for a2 than zaleplon. Therefore, pharmacologically Zopiclone is very similar to benzodiazepines.


After ingestion zopiclone is rapidly absorbed, its bioavailability is about 80%. The binding of zopiclone to plasma proteins is from 45 to 80%. Zopiclone rapidly and widely distributed in the tissues of the body, including the brain, and is excreted in urine, saliva and breast milk. Zopiclone is partially metabolized in the liver with the formation of an inactive N-demethylated derivative and its active N-oxide metabolite. In addition, approximately 50% of the administered dose is decarboxylated and discharged through the lungs. In urine, N-demethyl and N-oxide metabolites account for 30% of the initial dose. 7-10% of zopiclone is excreted from urine, which indicates an extensive metabolism of the drug before excretion. The terminal half-life (t1 / 2z) of zopiclone ranges from 3.5 to 6.5 hours. The pharmacokinetics of zopiclone in the human body are stereoselective. After oral administration of the racemic mixture, Cmax (time to peak plasma concentration), AUC (area under time-concentration curve in plasma), and t1 / 2z higher for dextrorotatory enantiomer, due to slower full elimination and smaller volume of distribution (with correction on bioavailability) compared with the levorotatory enantiomer. In urine, the concentrations of dextrorotatory enantiomers of metabolites of N-demethyl and N-oxide are higher than the concentrations of the corresponding antipodes. The pharmacokinetics of zopiclone varies with age and under the influence of renal and hepatic functions.


Zopiclone also interacts with trimipramine and caffeine. Alcohol in combination with zopiclone enhances its effect and undesirable effects, including significantly increasing the potential of a zopiclone overdose. [[erythromycin | Erythromycin]] increases the rate of absorption of zopiclone and prolongs the half-life of zopiclone, which leads to an increase in the concentration of the drug in the blood plasma and more pronounced effects. Itraconazole has an effect similar to erythromycin on the pharmacokinetics of Zopiclone. Elderly people may be particularly sensitive to drug interactions between erythromycin and itraconazole with zopiclone. It may be necessary to temporarily reduce the dosage with combined therapy, especially in the elderly. Rifampicin causes a significant decrease in the half-life of Zopiclone and peak plasma levels, leading to a decrease in the hypnotic effect of zopiclone. Phenytoin and carbamazepine can also provoke similar interactions. Ketoconazole and sulfafenazole interfere with the metabolism of zopiclone. Nefazodone interferes with the metabolism of zopiclone, causing an increase in the levels of Zopiclone and sedation the next day.


Zopiclone was developed and first introduced in 1986 by Rhone-Poulenc S.A., now part of Sanofi-Aventis, the main Zopiclone producer worldwide. Initially, the drug was marketed as an improved version of benzodiazepines, but a recent meta-analysis showed that zopiclone has no particular advantages over benzodiazepines in any of the accrued aspects. On April 4, 2005, the US Drug Enforcement Administration included zopiclone in List IV of substances, since the drug has the properties to be addictive, similar to benzodiazepines. Zopiclone, traditionally sold throughout the world, is a racemic mixture of two stereoisomers, only one of which is active. In 2005, Sepracor, a pharmaceutical company in Marlborough, Massachusetts, began selling an active Esso-cyclone stereoisomer called Lunesta in the United States. The consequence of this was the formulation of this drug, which is a generic in most countries of the world, under patent control in the United States. Although it was expected that the drug would be available in the form of generics by 2010, no generic drug on the market has yet been reported. However, Zopiclone is currently available as a non-proprietary drug in several European countries, as well as in Brazil, Canada and Hong Kong. The difference between Eszopiclone and Zopiclone is in dosage - the most active dose of the Eszopiclone derivative contains 3 mg of the therapeutic stereoisomer, whereas the highest dose of zopiclone (7.5 mg) contains 3.75 mg of the active stereoisomer. These two substances have not yet been investigated in comparative clinical trials to determine the presence of any potential clinical differences (in efficacy, side effects, dependence development potential, safety, etc.).

Recreational use

Zopiclone is a drug with the potential for abuse and drug escalation, drug addiction and drug dependence. Zopiclone is well known among drug addicts as a drug that causes addiction. The drug is taken orally and sometimes - intravenously and often in combination with alcohol to achieve a combined sedative hypnotic-alcoholic euphoria. Patients who abuse the drug are at risk of dependence. After long-term use of the drug in normal doses, symptoms of withdrawal symptoms can be observed, even after a gradual dose reduction. It is usually recommended to take Zopiclone no longer than 7-10 days, for reasons of possible dependence and tolerance to the drug. Perhaps the development of two types of drug dependence: abuse in recreational purposes, when the drug is taken to achieve "buzz", or the continued use of the drug without medical advice. Zopiclone may have a more pronounced potential for dependence development than benzodiazepines. Patients who have abused psychoactive substances in the past or who have mental disorders may be at high risk for Zopiclone abuse in high doses. Symptoms of dependence when abusing Zopiclone may include depression, dysphoria, feelings of hopelessness, slowing of thoughts, social isolation, anxiety, sexual anhedonia and nervousness. Zopiclone and other sedative hypnotics are often found in cases where drivers are suspected of driving while intoxicated. In such cases, other drugs are often found, including benzodiazepines and zolpidem. In many drivers, the level of the drug in the blood significantly exceeds the therapeutic dose and is often observed in combination with alcohol and other drugs. Benzodiazepines, zolpidem and zopiclone are associated with a high risk of abuse. Zopiclone, which, when taken at prescribed doses, causes mild side effects observed the day after the application, increases the risk of road traffic accidents by 50 percent. To reduce the risk of accidents, Zepiclone is recommended to use zaleplon or drugs. Zopiclone and other sleeping pills are sometimes used to commit criminal acts, such as sexual assault. Zopiclone has cross tolerance with barbiturates and can suppress signs of abstinence of barbiturates. Zopiclone is often used intravenously, and studies in monkeys have shown that such use is associated with a high risk of abuse. Zopiclone is one of the top ten drugs obtained with the use of false prescriptions in France. However, due to the distinctly bitter taste of the drug, it is unlikely that it will be used for criminal purposes, such as robbery and sexual assault. The tablets are covered with a special layer of film to mask the taste when swallowed, but when chewing this film collapses. In addition, the common side effect is a bitter, metallic taste after ingestion, so the person who took Zopiclone will probably know what is under the effect of this drug.


Zopiclone is sometimes used as a method of suicide. Zopiclone has a death rate similar to benzodiazepine (except for temazepam, which is toxic in overdose). Reports of deaths due to an overdose of Zopiclone, when taken alone or in combination with other medicines. Overdose zopiclone can be expressed by excessive sedation and a decrease in respiratory function up to coma and, possibly, death. Zopiclone in combination with alcohol, opiates or other CNS depressants can lead to a fatal overdose. With Zopiclone overdose, it is possible to take a benzodiazepine receptor antagonist flumazenil, which displaces zopiclone from the benzodiazepine binding site at the receptor, thereby facilitating the rapid elimination of zopiclone effects. In case of an overdose of Zopiclone in combination with piperazine, serious effects on the heart can also be observed. Evidence of death shows an increase in the number of deaths from Zopiclon overdose. Zopiclone, when taken alone, is usually not fatal, but in combination with alcohol or other drugs, such as opioids, or in patients with diseases of the respiratory system or liver, the risk of serious and fatal overdoses increases.

Detection in biological fluids

Zopiclone can be detected in the analysis of blood, plasma, urine, or by chromatography. Zopiclone concentrations in plasma for therapeutic use are usually less than 100 g / L, but often exceed 100 ?g / L in drivers of motor vehicles arrested for a decreased ability to drive vehicles and can exceed 1,000 ?g / l in patients with acute poisoning. Postmortem concentrations of the drug in the blood, as a rule, lie in the range 0.4-3.9 mg / l in the victims of acute fatal overdose.