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MEDSCI 204: Drug Assignment
Introduction
Zopiclone is a cyclopyrrolone derivative (1) which falls under a family of Non-benzodiazepine
hypnotic agents (2). Known by either one of its trade names Imovane or Zimovane (2),
zopiclone is found to have therapeutic actions on many psychophysical conditions but in
particular it is used to treat short-term insomnia (1). zopiclone was originally discovered and
introduced into the pharmaceutical market in the year 1986 by a French Pharmaceutical
Company “Rhone-Poulenc” which is now collectively a part of “Sanofi-Aventis” (2). The drug
is commonly administered orally (4) and studies have described improved absorption time
and greater hypnotic effect when patient had taken the zopiclone tablet in a standing
position rather than a supine position (4). Normal Prescription ranges per
administration/dosage is generally 7.5 mg (orally) (5) and is recommended that patients take
the drug 30-60 minutes prior to sleeping/bedtime (5). Dosage adjustments is a common
parameter to tailor for special population groups e.g. Elderlies and patients with Hepatic
insufficiency etc. (5). In the case of Dosage adjustments, patients are generally
recommended half of the standard dosage i.e. 3.75 mg (4) but this amount can be increased
up to a 7.5 mg if deemed necessary (3).
Despite being that of Non-benzodiazepine, zopiclone has exhibited similar pharmacological
characteristics as that of Benzodiazepine (4, 5). It has been shown that zopiclone achieves it
therapeutic actions through the agonist binding to 𝛾-aminobutyric acid (GABA) receptors and
thereby acts to enhance the inhibitory effects of the GABA neurotransmitter (6). With this
being said, Zopiclone agonist binding is not orthosteric to that of the benzodiazepine binding
sites but rather it associates to binding sites in close proximity to the Benzodiazepine-
receptor complex (5). As a consequence of enhancing the binding of GABA to the GABA-
chloride ionophore complex, zopiclone has produced pharmacological effects similar to that
of Benzodiazepine such as Anxiolytic, anticonvulsant and muscle relaxant properties (5).
Evidence on zopiclone dependency in the literatures have been described as being
“sporadic” (2). Nevertheless, available data has suggested the increased risk of dependency
and tolerance of zopiclone in conjunction with individual who have had a history of alcohol
MEDSCI 204: Drug Assignment
Figure 1. Alignment of zopiclone with GABAA receptor pharmacophore (12)
and drug addiction. Furthermore, studies have also come to acknowledge potential in
zopiclone abuse in replacement for recreational drugs such as Heroin (2).
Composition/formulation and structure/nomenclature
In clinical practice, zopiclone is only available in its oral formulation; however there has been
reported cases of drug abuse whereby individuals have actively attempted to inject the drug
via intravenous methods (7), these situations however, are very scant compared to the
relative to the common method of zopiclone administration. The standard dosage
recommendation for zopiclone is 7.5 mg (tablet/oral form) prior to going to bed (8). In the
case of elderlies or individuals suffering from moderate-to-severe hepatic impairment it is
recommended that the starting dosage to be halved, though incremental changes can be
made along the process of treatment. (8)
Although zopiclone is a derivative of the cyclopyrrolone family i.e. unrelated to the
benzodiazepine family, it was suggested through studies that zopiclone acted as a full
agonist on the benzodiazepine GABAA receptors to induce corresponding hypnotic effects
(9). This observation lead to believe that there are certain degrees of chemical similarities of
zopiclone and other hypnotic
agents (of similar molecular
target) in comparison to the
class of benzodiazepine
drugs. Zopiclone has a
molecular weight of 388.82
and a chemical formula of
C17H17ClN6O3 (10). Studies
conducted regarding the
receptor site of the GABAA receptor in relation to its respective hypnotic agents have
revealed the presence of a pharmacophore. A pharmacophore describes the characteristic
features of a molecular complex which is vital for recognition and binding to that active site.
(11)
Figure 1. Demonstrates the aligning of the zopiclone molecule with the pharmacophore of
the benzodiazepine receptor site. The pyridine moiety of zopiclone is shown to interact with
region L1 of the receptor, the lone paired electron of carbonyl oxygen interacted with H1
(through hydrogen bonding) and finally the lone pair in amide carbonyl oxygen formed the
second hydrogen bond with H2 receptor of the protein complex (12). In order to achieve
therapeutic as well as physiological effects via GABA mediated receptors, the drug must fulfil
MEDSCI 204: Drug Assignment
the various parameters relating to the pharmacophore. The drug must conform to the
Hydrogen accepting sites and lipophilic binding sites of the pharmacophore as well as
achieving similar volume profiles at respective binding sites as that of benzodiazepine.
Drugs which fall under these categories i.e. share similarities are drugs such as zopiclone,
zolpidem and other Z-class drugs. (12)
Absorption, distribution, metabolism and excretion
Extensive research has been conducted on the pharmacokinetic aspect of the drug
Zopiclone. Initial studies conducted by G. Callie, (1984) (13) suggested a rapid absorption
from the gastrointestinal tract that reaches a peak plasma concentration ranging from 54 to
86 𝜇g/L within the course of 0.5 to 4 hours following administration (13). Although Callie’s
data were established on the basis of data extrapolation from only a few plasma samples, it
suggested for unprecedented data on the pharmacokinetic properties of the drug. More
recent data acquired have come to suggest findings that corresponded to prior research
results; time peak of Zopiclone (tmax) was measured to occur within 1 to 2 hours following
administration and reaches a maximal peak plasma concentration of 131 𝜇g/L (under
administration of a standard 7.5 mg dosage, tablet form) (7). An absorption rate constant
was calculated to be at that of 1.3 h-1 and is associated with an absorption half-life of 0.52
hours. Oral bioavailability of the drug as compared to that of an index value (intravenous
injection) measures a substantially high value of 75-80% and is therefore implicative that
first-pass metabolism is diminished in Zopiclone absorption and distribution (7) (13). Factors
such as high-fat meal prior to drug intake does not affect AUC but it is causal of a reduction
in peak plasma concentration and delay in occurrence which is speculated to ultimately alter
the onset of the efficacy of the drug (14). Furthermore, it has also been concluded that
administration in a supine position results in a minor delay in drug absorption, but this delay
is insubstantial of holding any clinical significance. (14)
It is suggested that Zopiclone has a weak affinity to plasma protein. With only 52-59% of the
drug being bound to plasma proteins, this indicates that there is no apparent selective
interaction between the drug and red blood cells. With an apparent Volume distribution value
ranging between 92L and 140L (mean: 132 L) (7), as well as the observational data that
suggested that 50% of participants had come to experience the desired effect of the drug
within 30 minutes since administration (7)(13) , it may be conclusive that Zopiclone is rapidly
distributed within the circulation and allows for relatively fast onset of its hypnotic effects.
Furthermore, the rapid distribution of Zopiclone is manifested in saliva samples 15 minutes
MEDSCI 204: Drug Assignment
into the time since administration such that salivary Zopiclone concentrations have exceeded
that in the plasma circulation; this finding could potentially suggest for the bitter taste upon
ingestion caused by salivary excretion of the drug (12). Using data from animal experiments,
it was suggested that highest levels of Zopiclone accumulation occurred at the level of
muscle, liver, fat tissue and kidney rather than in solid organs; this observation is also
confirmed through post-mortem examinations to which it was seen that there was an
insignificant quantity of Zopiclone distributed at the level of the solid organs but rather, a
much higher concentration in plasma. (13)
Zopiclone clearance is estimated to occur at rates between 13.9-18.5 L/h and this
accompanied with an elimination half-life (t1/2) of approximately 5 hours (range: 3.5-6.5
hours) (12). In contrast to a large majority of traditional benzodiazepine drugs, the
elimination half-life of Zopiclone and its metabolites are significantly lower; this reduces
potential for the prolonged after-effect that patients may experience due to residual drug in
the system which may adversely affect cognitive and psychomotor functions the next day.
The above pharmacokinetic parameters regarding half-life and clearance are those valid to a
healthy individual; it is observed that in elderlies (>65 years of age), there is an apparent
shift in parameters such as increase in AUC by 40% and a higher half-life of 9 hours
(compared to the mean value of 5 hours) and these can be ultimately attributed to changes
to the functional architecture of the liver and kidney with age (13).
Taken into account that the bioavailability of Zopiclone has achieved consistent values
between 75-80% from historic and current data, it can be assumed that the degree of first
pass metabolism is very much diminished. Body fluid samples have come to suggest that
only 7% of the initial dosage (parent drug) is excreted via the urine and the rest is mainly
metabolised prior to any elimination processes. The drug is primarily metabolised in the liver
via three biotransformation pathways: oxidation, decarboxylation and demethylation.
Approximately 50% of the initial dosage undergoes decarboxylation reactions and is
eliminated as carbon dioxide through the lungs (7)(12)(13). The two main urinary metabolites
of Zopiclone are the active Zopiclone-N-oxide (which contributes to ~12% of dose) and the
inactive/inert metabolite: N-desmethyl-zopiclone (which contributes to ~16% of dose). The
biotransformation of Zopiclone into these two urinary metabolites are mediated by the
cytochrome P450 isoenzymes: CYP34A, and to a lesser degree: CYP2C8 (7).As discussed
above, only an estimated 5-7% of the initial parent dose is excreted via the urine unchanged
and approximately 16% is presented in the faeces (biliary excretion). Excretion is also
evident via salivary secretion and it is this which contributes to the bitter, metallic after-taste
reported by patients upon ingestion; Zopiclone is also distributed into breast milk. The
MEDSCI 204: Drug Assignment
approximated half-life of the two metabolite derivatives of Zopiclone: N-oxide derivative and
N-desmethyl derivate measure at 4.5 hours and 7.5 hours respectively; The N-oxide derivate
of Zopiclone although being an active metabolite, has a lesser extent in terms of
pharmacological activity compared to Zopiclone. (7)
Mechanism of action/ Therapeutic applications
Zopiclone is often regarded to as an alternative to the classic Benzodiazepine drug due to a
decreased elimination half-life of both itself and its constituting metabolites (12). Though
differing in chemical structure, Zopiclone shares similar pharmacological profiles as seen in
Benzodiazepine, achieving hypnotic, anxiolytic, myorelaxant, sedative and anticonvulsant
effects which is exploited to effectively target short-term (acute) insomnia (4)(7). In terms of
clinical relevance, Zopiclone is often regarded as being that superior to the traditional
benzodiazepines because of reduced concerns in tolerance and dependence profiles (7)(9);
it is often offered as an alternative to patients suffering from benzodiazepine withdrawal-
induced rebound insomnia (15)
Hypnotic agents are thought to induce their pharmacological properties through allosteric
modulation of the ionotropic GABAA receptor complexes, binding at the interface between
the γ and α subunits of the receptor (9). GABA being one of the most widespread inhibitory
neurotransmitters present in the CNS, has its actions mediated by 2 types of receptors: the
ionotropic GABAA receptor and the slower-acting metabotropic GABAC receptor (16). Studies
have suggested that the traditional hypnotic medications act through GABAA receptors, and
their presence in the system does not affect normal GABAC receptor functions. It is believed
that zopiclone acts to potentiate GABAA receptor functions, such that it mediates the influx of
Cl- ions into the neuronal membrane and thus hyperpolarizing and diminishes neuronal
firing. For some time, it was hypothesized that zopiclone shared the same binding domains
as that of the classic benzodiazepines (9). However with the addition of novel research
techniques such as photoaffinity labelling of hypnotic analogues as well as mutagenesis of
receptor amino acid residues it was suggested that it may be possible that zopiclone
interacts with slightly different amino acids and thereby producing a distinctive variant in
terms of receptor function following ligand binding (11). Characterization of the GABAA
pharmacophore revealed that there are some structural requirements such as lipophilic
regions and lone pair oxygen molecules which are needed to satisfy L and H regions
respectively; photolabelling has also revealed an important Histidine-101 side chain residue
believed to be crucial for the recognition of GABAA agonists (11)(9) . Despite some
similarities in interaction, it is suggested via a model of ligand binding (9) that
cyclopyrrolones interact at shallower depths of the receptor cleft compared to that of the
MEDSCI 204: Drug Assignment
benzodiazepine agonists. This has caused researchers to suggest that it is these distinct
interactions of zopiclone that establishes it highly efficacious and superior therapeutic effect
compared to benzodiazepine.
1) Heterogeneity of GABAA receptor subtype
The differential expression of GABAA receptor phenotypes allows one to map out the
abundance of receptor subtypes in respect to both location and function. The most
widespread subtype in the CNS is the 𝛼1𝛽2𝛾2 receptor and it has been speculated
that it is this 𝛾2 subunit within the receptor complex that contributes a determining
role in neuronal inhibition of the central nervous system (7). Despite a non-specific
activation of all 𝛼 subtypes, zopiclone exhibits particularly high affinity binding profiles
to the 𝛼1 subtype (9). Together, it may be suggested that interaction due to high-
affinity binding profile of zopiclone allows for it to exhibit high therapeutic efficacy.
(9)(11)
2) GABA shift
GABA shift describes a process by which the presence of GABA at receptor sites
enhances mediation of compound pertaining to an intrinsic potentiation property (and
vice versa) (9). It was demonstrated that incubation of GABA at their binding sites
increased benzodiazepine affinity profiles. Ironically, it is also this theory of GABA
shift which helps to elucidate the loss of sensitivity towards benzodiazepine
suggesting that chronic administration of benzodiazepine is responsible for the loss
of GABA shift (9). In contrast to the above, zopiclone is believed to be the only full
agonist showing exception to GABA shifting; it does not undergo conversion into a
partial inverse agonist and therefore makes it less susceptible to the development of
tolerance and dependence. (9)
Upon examination of zopiclone’s clinical efficacy, it has been revealed from EEG recordings
that administration of zopiclone prior to going to sleep decreases the period of Non-REM
sleep while prolonging the time of stage 2 REM sleep (7). Comparative trials concerning
hypnotic efficacy has shown (in most cases) that zopiclone is either superior or equal to
most hypnotics in terms of treatment for insomnia. When compared to Diazepam, it was
revealed that only zopiclone administration significantly prolonged total sleep time (13.5% for
7.5 mg dosage and 26.6% for 15 mg dosage) (4). Zopiclone administration (7.5mg/day) for 4
weeks revealed a slightly more efficacious result compared to that of flunitrazepam
(1mg/day) for sleep quality and day-time wellbeing (4). These parameters have all come to
suggest that zopiclone is much more efficacious especially in treating short-term insomnia.
MEDSCI 204: Drug Assignment
Currently, zopiclone is not used in combination with any other drug; there however are drug
interactions which may produce contraindications (see below). Although there have been
particular national restrictions governing availability, therapeutic monitoring is not required as
of this stage. (7)
Adverse effects/contraindication/drug interactions
Studies were conducted to investigate the residual effects of zopiclone compared to placebo
on the effects of driving performance following administration of the standard 7.5 mg oral
dose. It is believed that the mechanisms underlying residual daytime sedation is due to the
hypnotic effects elicited by both the drug itself as well the metabolite zopiclone-N-oxide
which, on its own is believed to have a weak hypnotic effect (14). Comparisons between
healthy individuals reported of having no problems relating to insomnia and individuals who
have had problems of chronic insomnia revealed that the effects of residual daytime
sedation was less pronounced (if even present) in the chronic hypnotic users compared to
that of the healthy infrequent users of zopiclone (17). In the cohort of chronic zopiclone
users, it is suggested that daytime awareness and alertness is heightened following intake in
the previous night before bedtime. In contrast, the opposite observation was reported in the
cohort of healthy, infrequent users, suggesting a significant impairment in driving
performance due to effects of residual daytime sedation. It is believed that the factor
contributing to these two opposing observations is the overestimation of the effects of
residual sedation on chronic hypnotic users as they have already developed a degree of
tolerance to the drug (zopiclone) (17). Interestingly, when zopiclone is removed from the lists
of medication given to people of the chronic users, effects of withdrawal had significantly
impacted on these performance parameters. In comparison however, it is revealed that
performance in the highway test for both cohorts was not seriously impaired and this can be
attributed to the notion that individuals are to compensate for any residual sleepiness and
aftereffects when performing simple and non-complex tasks. (17)
However, the most commonly reported adverse effect of zopiclone is the metallic after taste
which is associated to post-administration of the drug (7), reported by 10% of its recipients. It
is believed that this adverse effect is attributed to the fact that zopiclone is rapidly distributed
across the circulation and partial excretion has been revealed to occur at the level of the
salivary glands (7)(14). Because zopiclone acts as a full agonist on Benzodiazepine GABAA
receptors, mechanisms of dependence and withdrawal-induced rebound insomnia occurs via
similar mechanism as that of benzodiazepine; with this being said, zopiclone’s potential of
MEDSCI 204: Drug Assignment
dependence and tolerance is greatly reduced compared to the traditional hypnotic agents
due to its short-acting purpose (9)(7). In the human body, dependence is largely the effects
of what is understood as being the “reward-system” in which the individual gives a reason to
a particular activity e.g. eating, drinking to a pleasurable after-sensation (18). Chronic use of
zopiclone against recommended dosage time frame will induce the down regulation of
GABAA receptors as well as up regulation receptors off antagonist effect to the
neurotransmitter. In the case whereby the patient removes zopiclone from their list of
medication(s), symptoms mirroring the drug’s original effect will occur; symptoms include:
nightmares, hypnogogic hallucinations, anxiety and muscle spasms etc. Furthermore,
shifting the mode of zopiclone and other hypnotics to that of an inverse agonist state will
heighten sensitivity of the brain towards excitatory drugs or stimuli, thereby causing
excitotoxicity in the CSN; this explains the occurrence of rebound insomnia in some patient
profiles. (19)
Patients suffering from hepatic insufficiency will have the processes by which zopiclone is
metabolised, compromised. As a result, it has been reported that those with hepatic
insufficiency have a prolonged t1/2 (by twice the normal length) (14), accompanied by a
decrease in the respective concentrations of its metabolites. Dosage adjustment is thereby
required in patient with severe liver diseases as well as in elderly patients who experience
moderate-to-severe hepatic diseases; beginning with a starting dosage of 3.75 mg. (7)(4)
Furthermore, it has been suggested that many individuals with a history in drug-abuse or
psychiatric disorders have a higher risk of developing dependence or recreational abuse. A
study conducted on 297 drug addicts had revealed that among the 88.5% of users that had
reported of taking the drug for sleep-enhancing effects, 56.7% had reported that they
actively take the drug to feel better whereas 22.9% revealed that they took the drug in order
to achieve the feeling of getting “high” (7).
In a case regarding a patient undergoing cross-treatment with both zopiclone and
nefazodone (anti-depressant), it was reported that the patient experienced symptoms such
as a morning drowsiness and the removal of zopiclone from her medication resulted in
decrease plasma levels of zopiclone (from 107 to 16.9 ng/mL). It is believed that nefazodone
as well other drugs such as cimetidine or erythromycin are potent inhibitors of Cytochrome
P450 enzymes (primary role in drug metabolism); inhibition of CYP450 will thereby prolong
the time which the active form of the drug persists in the body. Conversely, it is suggested
that potent inducers of CYP34A such as rifampicin and phenytoin etc. potentially interfere
with zopiclone efficacy. (7)
MEDSCI 204: Drug Assignment
Funding and marketing issues
Since being introduced into the pharmaceutical market, zopiclone’s hypnotic effects have
been exploited for drug abuse purposes. There has been reported cases whereby
individuals undergo active incremental changes of dosage, reaching a summated daily
dosage of 105 mg which was taken as separated in 2-3 oral tablet forms (7). A study
branching off a Methadone program in Iceland had revealed that amongst the 38 patients
taking zopiclone, 16 had suggested that their misuse can be attributed to the degree of
tranquilization induced by the drug; out of these 16 patients, one had reported of attempting
to inject the drug. In addition to these reported cases of drug abuse, Zopiclone misuse has
also been associated with drug-facilitated crimes such as sexual assaults or robbery (7).
Recently, surveys have shown that there is an increase incidence whereby zopiclone is
purchased through false prescriptions or purchased on the street, as suggested by 56.7% of
zopiclone users. Other cases of the recreational use of zopiclone has been attributed to
factors such as induction of euphoria or even to disinhibit an anxiolytic effect. Ultimately,
these recurring incidences has established zopiclone as a substance for drug abuse. (7)
Out of the 59 countries that responded to the WHO survey on zopiclone, 34 countries
currently authorize the market distribution and availability of the drug to the public (7);
however one country has also revealed that the authorization status was shortly withdrawn
following its induction to the public (7). On a national scale, zopiclone is currently subsidized
by the country’s PHARMAC schedule. However with this being said, Apo-Zopiclone (7.5 mg,
film coated, 500 tablet, bottled) and Zopiclone actavis are the only brands of zopiclone that is
currently fully subsidized by the government at $11.90 per unit and $8.99 per unit
respectively (20). On the 4th of April, 2005, the United States had placed zopiclone and its
isomers in schedule IV as a part of the Controlled substances Act by the Drug enforcement
administration due arisen incidences of abuse (7). Along with the United States, Zopiclone is
also placed under control in France as it is a one of the top ten substances of falsified
prescription and illicit manufacturing (7). Other countries that have placed Zopiclone under
control are Mauritius and Turkey. However, in general, the act of limiting zopiclone’s market
availability on an international scale has caused many countries to respond in a very
sceptical way. In the 2005 WHO questionnaire regarding the substance, it was suggested by
countries such as China, Japan and Myanmar etc. that international governance of zopiclone
control will greatly affect the medical availability of the drug, especially in remote areas and
thereby changing the mode of circulation with the market. (7)
MEDSCI 204: Drug Assignment
Part B – Would you take this Drug?
As a novel hypnotic agent induced into the market during the late 20th century (1986) (2),
zopiclone has received a diversity of responses, a majority being that of a supportive nature.
Personally, I value the quality of my sleep to a very high extent as I understand that the
quantity as well as quality of sleep will have a profound effect in terms of my various
performance parameters during in the next day. As a university student, I am often obligated
to various work and academic commitments during the week and it is this stress which has
overlaid a huge burden onto my sleep routine and quality. Studies have been conducted to
show the positive correlation between the amount of stress to the quality and quantity of
sleep for an individual; on top of this, sleep deprivation is also associated to a decline in
attentiveness and working memory functions as well as other symptoms such as physical
fatigue and emotional instability (21). With all these factors summated, I believe that it is
crucially important for me to undergo immediate treatment in the case of short-term, acute
insomnia as this will ensure that my ability to achieve maximal performance in both an
academic and work environment will not be hindered.
Zopiclone is a short-term acting hypnotic agent that has had its clinical efficacy proven to be
either equal if not superior to most of the traditional benzodiazepine hypnotic agents (9)(7).
In addition, it is also suggested through clinical trials and observational studies that the
potential for dependence and tolerance, though existent, is relatively much lower than that of
the traditional hypnotics. The main therapeutic target in zopiclone treatment is to improve
sleep duration as well as quality in individuals suffering from acute insomnia (4). Side-effects
relating to zopiclone are that of an anxiolytic, myorelaxant, and sedative property (4);
although these induced side-effects will not be the determining factors impacting my decision
of whether I would take this drug or not, its “tranquilizing and calming” (7) effect could
potentially be used to my advantage (In complement to its primary effect), providing that
drug usage is done in careful moderation and not recreationally. Conclusively, during the
transient periods of insomnia, I would consider taking the drug in order to prevent the
development of the range of manifesting effects caused by sleep deprivation.
As mentioned briefly above, there are still cases of reported incidences of tolerance and
other adverse effect (7)(2). However, the pharmacokinetics of zopiclone and its clinically
safety has been proven to be superior to the traditional hypnotics due to factors such as
MEDSCI 204: Drug Assignment
decreased half-life and improved immediacy of its therapeutic efficacy. Surveys conducted
relating to the adverse effects of zopiclone are relatively much lower compared to its
comparative drugs and therefore it may be implied that usage of the drug is safe providing
moderate use stemming from a non-abuse intention. However, one factor that I may have to
take into consideration is zopiclone’s contraindications with alcohol (4). Alcohol is known as
a CNS depressant and consumption with zopiclone could potentially induce toxic and life-
threatening effects. As a result, if I was to use zopiclone as means of sleep medication, extra
caution must be taken such that I do not take it following a nights out or other activities
involving alcohol consumption.
Apo-Zopiclone is currently subsidized by the New Zealand government (7.5 mg, tablet, 500
tablets/bottle) at $11.90 per unit. Zopiclone activas is also subsidized containing the same
amount as that of Apo-Zopiclone but set at a price of $8.99 (21). This price is economically
affordable taking into account of my personal income; 500 tablets/bottle is however, in
excess considering the main therapeutic target is to treat short-term insomnia. With this
being said, expiry date which is generally 18 months, should be examined by infrequent
users, prior to consumption.
Clinical efficacy of zopiclone has been proven to be either equal or superior to that of the
classic benzodiazepine drugs; zopiclone is also often used as an alternative medication for
patients whom have developed tolerance or dependence to benzodiazepines (4)(7). Ethical
issues surrounding zopiclone is quite controversial but relatively minor in comparison to
issues relating other drugs. Restrictions in public distribution is thought to compromise
medical availability and therefore stemming other illicit forms of manufacturing and
purchasing (7). However, non-restricted availability will also conversely result in zopiclone
being used for abusive purposes (7). These ethical issues, however, do not apply to me
personally so will not impact on my decision of using the drug.
MEDSCI 204: Drug Assignment
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