|Summary sheet: Zopiclone|
|Molecular structure of zopiclone|
|Common names||Zimovane, Imovane|
|Systematic name||(RS)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate|
|Routes of Administration|
Zopiclone (commonly sold under the trade names Zimovane and Imovane) is a pharmaceutical non-benzodiazepine hypnotic agent of the cyclopyrrolone chemical class that is primarily used in the treatment of insomnia. Zopiclone is known to belong to a family of drugs colloquially known as "Z-drug". Other Z-drugs include zaleplon (Sonata) and zolpidem (Ambien and AmbienCR).
It is thought to increase the normal neurotransmission of the neurotransmitter GABA in the central nervous system in a similar yet distinct way to the activity of benzodiazepines. As zopiclone displays heavy sedating effects, it is has been approved for and is commonly sold as a sleeping pill.
While "Z-drugs" were initially thought to have less misuse potential than benzodiazepines, this appraisal has shifted somewhat in the last few years as a number of cases of addiction and habituation have been observed. Zopiclone, like all "Z-drugs", is recommended to be taken on a short-term basis -- usually a week or less. Daily or continuous use of the drug is usually not advised.
- 1 Chemistry
- 2 Pharmacology
- 3 Subjective effects
- 4 Toxicity and harm potential
- 5 Legal status
- 6 See also
- 7 External links
- 8 References
Zopiclone is a hypnotic nonbenzodiazepine drug of the cyclopyrrolone class. Zopiclone and its closely related dextrorotatory S-stereoisomer eszopiclone (Lunesta) are the most popular and available cyclopyrrolone drugs. This class of drugs is named for having a pyrrolone core, a five-membered ring with a nitrogen constituent (pyrrole) and a ketone group (-one).
The ketone group found in zopiclone is located at R5 of the pyrrolone ring. Zopiclone contains four nitrogenous rings including pyrrolone. Fused to the pyrrolone core is a pyrazine ring, a six-membered aromatic ring with two nitrogen substituents. The two rings are fused at R3 and R4. This bicylic core is called a pyrollopyrazine. Bound to the nitrogen group of the pyrrolone at R6 is a substituted pyridine ring. Pyridine is six-membered unsaturated ring with one nitrogen group. The pyridine ring of zopiclone is substituted at R5 with a chlorine group.
The final ring of zopiclone is a piperazine ring. Piperazine is a six-membered saturated ring with two nitrogen constituents; in this case, it is substituted at R4 with a methyl group. This piperazine ring is connected to the pyrrolone core of zopiclone at R7 through a carboxylate group.
Zopiclone, although structurally different from benzodiazepines, shares an almost identical pharmacological profile to them. Its mechanism of action works by binding to the same site as benzodiazepines and acts as a full agonist, which in turn positively modulates benzodiazepine-sensitive GABAA receptors and enhances GABA binding at the GABAA receptors to produce zopiclone's pharmacological properties. Since GABA functions as the brain's predominant inhibitory neurotransmitter, this activation of receptors results in the sedative and anxiolytic effects of zopiclone.
In comparison to other compounds of a similar nature such as benzodiazepines, this compound is commonly reported to present significantly more amnesic and disinhibiting effects similar to alcohol. The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include injury or death.
- Sedation - In terms of energy level alterations, zopiclone is extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit or lay down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and can eventually become powerful enough to force a person into complete unconsciousness regardless of where they are or what they are doing at that moment.
- Respiratory depression
- Muscle relaxation
- Motor control loss
- Gustatory hallucinations - Zopiclone is known to cause a lingering 'metallic' taste in the mouth and throat which may persist into the next day, and often changes the flavor of any food or drink the person consumes.
- Acuity suppression
- Drifting - Visual distortions in the form of drifting, breathing, melting and flowing are the most prominent visual effects of this substance and typically occur at strong doses, or when the user resists the urge to sleep. They are similar to the distortions seen on zolpidem and are usually less pronounced than those caused by deliriants. These distortions are most prominent in low lighting.
- External hallucinations - At very high doses, zopiclone can produce external hallucinations that are similar to, but less pronounced than deliriants.
The cognitive effects of zopiclone can be broken down into several components which progressively intensify proportional to dosage. The general head space of zopiclone is described by many as one of intense sedation, decreased inhibition and severe amnesia. It produces a large number of cognitive effects typical of most GABA-ergic depressants.
- Amnesia - Compared to benzodiazepines, zopiclone can produce amnesia at much lower doses. One may potentially not remember exactly what happened while under the influence of a high dose.
- Anxiety suppression
- Thought deceleration
- Analysis suppression
- Euphoria - Some users report euphoria from zopiclone, although this is short lived and usually exclusive to the onset of the experience and often followed by emotion suppression.
- Emotion suppression - While zopiclone primarily suppresses anxiety, it also supresses other emotions in a similar but less intense fashion to antipsychotics.
- Time compression - This effect is mostly noticable while under the influence of a high dose.
- Self harm - Self-harming behavior has been reported under the influence of high doses, although this is likely due to individual factors as opposed to pharmacological action.
- Compulsive redosing
There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
Toxicity and harm potential
By itself, zopiclone likely has a low toxicity relative to dose. However, it is potentially lethal when mixed with depressants like benzodiazepines, alcohol or opioids. When combined with one or several of these drugs the already existing chance of a having a "black-out" is significantly increased, leaving the user with very little to no memory of the events that occurred whilst under the influence of zopiclone alone or combined with most other CNS depressants. Users have reported taking zopiclone in combination with alcohol in an attempt to treat hangovers with varying degrees of success.
It is strongly recommended that one use harm reduction practices when using this substance.
Zopiclone is capable of resulting in death at extremley high doses and is sometimes used as a method of suicide. It has a similar fatality index as benzodiazepine drugs, apart from temazepam, which is particularly toxic in overdose.
An overdose of zopiclone may present with excessive sedation and depressed respiratory function that may progress to coma and possibly death. Zopiclone combined with alcohol, opiates, or other central nervous system depressants may be even more likely to lead to fatal overdoses. Zopiclone overdoses can be treated with the benzodiazepine receptor antagonist flumazenil, which displaces zopiclone from its binding site on the benzodiazepine receptor, thereby rapidly reversing its effects. Serious effects on the heart may also occur from a zopiclone overdose when combined with piperazine.
Tolerance and addiction potential
Zopiclone is extremely physically and psychologically addictive. This compound may have an even greater addictive potential than benzodiazepines and has been described as a "benzodiazepine in disguise".
Tolerance will develop to the sedative-hypnotic effects within a couple of weeks of daily use. After cessation, the tolerance returns to baseline in 7 - 14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.
Zopiclone presents cross-tolerance with all benzodiazepines, meaning that after its consumption benzodiazepines and most other GABAgenic depressants will have a reduced effect. Alcohol has cross tolerance with GABAA receptor positive modulators such as the benzodiazepines and the nonbenzodiazepine drugs. For this reason, alcoholics or recovering alcoholics may be at increased risk of physical dependence on zopiclone. It should be avoided in those with a history of alcoholism or drug misuse.
Discontinuation and withdrawal
Physical dependence, recreational abuse and withdrawal syndromes similar to those seen in benzodiazepine withdrawal are frequently encountered. Due to the risk of tolerance and physical dependence, zopiclone is only recommended for short-term relief of insomnia, or alternatively, long-term infrequent use. Abrupt withdrawal, particularly with prolonged and high doses, can (in severe cases) cause seizures and delirium.Withdrawal symptoms included anxiety, tachycardia, tremors, sweats, flushes, palpitations, derealisation, and further insomnia. Suspected withdrawal convulsions during detoxification from zopiclone have been reported, but the individual was a high-dose zopiclone misuser.
If zopiclone has been taken for more than a few weeks, then the medication should be gradually reduced or preferably crossed over to an equivalent dose of diazepam (Valium) which has a much longer half-life, making withdrawal easier. One should then gradually taper the dose over a period of several months to avoid extremely severe and unpleasant withdrawal symptoms which can last up to two years after withdrawal if the withdrawal is done too abruptly.
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
- Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
- Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
This legality section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
- United States: On April 4, 2005, the U.S. Drug Enforcement Administration listed zopiclone under Schedule IV due to evidence that the drug has addictive properties similar to benzodiazepines.
- United Kingdom: Zopiclone has been a class C drug since June 2014. It is illegal to possess (without a legitimate prescription), supply, produce or import.
- Australia: Zopiclone is prescription only.
- Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- Effects of zopiclone and temazepam on sleep, behaviour and mood during the day (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2744064
- Zopiclone fatality in a hospitalized patient (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9068198
- Detection and quantification of the hypnotic zopiclone, connected with an uncommon case of drowning (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8939015
- Relative toxicity of benzodiazepines in overdose (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9068198
- Buckley NA, Dawson AH, Whyte IM, McManus P, Ferguson N.Correlations between prescriptions and drugs taken in self-poisoning: Implications for prescribers and drug regulation.Med J Aust (in press)
- Relative toxicity of benzodiazepines in overdose
- Analysis of zopiclone (Imovane) in postmortem specimens by GC-MS and HPLC with diode-array detection (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8837952
- An autopsy case of poisoning by neuropsychopharmaceuticals including zopiclone (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9893443
- Two cases of fatal zopiclone overdose (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8868406
- Zopiclone overdose responsive to flumazenil (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16235515
- Zopiclone poisoning: tissue distribution and potential for postmortem diffusion (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8039775
- First-degree heart block caused by voluntary zopiclone poisoning (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2353332
- Auriculo-ventricular block during voluntary poisoning with zopiclone (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2814922
- Dart, Richard C. (2003). Medical Toxicology. p. 889. ISBN 978-0-7817-2845-4.
- Adverse effects of zopiclone (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9656789
- Imovane--a benzodiazepine in disguise (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8321452
- The role of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to test blood and urine samples for the toxicological investigation of drug-facilitated crimes (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18367985
- Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/7862917
- Evaluation of zopiclone physical dependence liability in normal volunteers (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6669632
- An assessment of short-acting hypnotics (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/8573298
- Hypnotic dependence: zolpidem and zopiclone too (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11503851
- Zopiclone withdrawal: an unusual cause of delirium in the elderly (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16107464
- Physical dependence on zopiclone: case reports (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9462317
- Misuse of zopiclone and convulsions during withdrawal (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/1754610
- A case of primary zopiclone dependence (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/11450624
- BENZODIAZEPINES: HOW THEY WORK AND HOW TO WITHDRAW | http://www.benzo.org.uk/manual/
- The Misuse of Drugs Act 1971 (Ketamine etc.) (Amendment) Order 2014 (Legislation.gov.uk) | http://www.legislation.gov.uk/uksi/2014/1106/contents/made