Zopiclone

Zopiclone
The skeletal formula of zopiclone
Chemical Nomenclature
Common names	Zimovane, Imovane
Substitutive name	Zopiclone
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
Class Membership
Psychoactive class	Depressant
Chemical class	Nonbenzodiazepine (Z-Drug)
Routes of Administration
Oral Dosage WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. Bioavailability 52-59% Common 3 - 7 mg Duration Total 6 - 9 hours

Summary sheet: Zopiclone

Zopiclone (brand names Zimovane and Imovane) is a non-benzodiazepine hypnotic agent used in the treatment of insomnia. It is a cyclopyrrolone, which increases the normal transmission of the neurotransmitter GABA in the central nervous system, similarly, yet differently, to the mechanism of benzodiazepines. As zopiclone is sedating, it is marketed as a sleeping pill.

Zopiclone is known colloquially as a "Z-drug." Other Z-drugs include zaleplon (Sonata) and zolpidem (Ambien and AmbienCR). They were initially thought to be less addictive and/or habit-forming than benzodiazepines. However, this appraisal has shifted somewhat in the last few years as cases of addiction and habituation have been presented. Zopiclone is recommended to be taken on a short-term basis, usually a week or less. Daily or continuous use of the drug is not usually advised.

Chemistry

Zopiclone is a hypnotic nonbenzodiazepine drug of the cyclopyrrolone class. Zopiclone and its closely related dextrorotatory stereoisomer eszopiclone (Lunesta) are the most available cyclopyrrolone drugs. This class of drugs is named for having a pyrrolone constituent, 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.

Pharmacology

Zopiclone, although molecularly different from benzodiazepines, shares an almost identical pharmacological profile as 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.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

Physical effects

The physical effects of zopiclone can be broken down into several components which progressively intensify proportional to dosage. These are described below and generally include:

• 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 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 eventually becomes powerful enough to force a person into complete unconsciousness.
• Respiratory depression
• Muscle relaxation
• Dizziness
• Motor control loss

Cognitive effects

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 and decreased inhibition. It contains a large number of typical depressant cognitive effects.

The most prominent of these cognitive effects generally include:

• Amnesia
• Anxiety suppression
• Thought deceleration
• Disinhibition
• Information processing suppression

Toxicity and harm potential

Lethal dosage

Zopiclone is capable of resulting in death at appropriately 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 may have an even greater addictive potential than benzodiazepines and has been described as a "benzodiazepine in disguise". Tolerance to the effects of zopiclone can develop after a few weeks.

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.

Zopiclone is cross-tolerant with benzodiazepines. 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.

Legal issues

• U.S.: 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.
• U.K.: The drug is prescription only.
• Australia: Zopiclone is prescription only.

See also

• Responsible use
• Benzodiazepine
• Depressants
• Zopiclone (Wikipedia)