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PubMed1999

Different effects of L-type and T-type calcium channel blockers on the hypnotic potency of triazolam and zolpidem in rats.

We examined the effects of an L-type Ca2+ channel blocker, nilvadipine (0.5 and 2.0 mg/kg), and that of a T-type Ca2+ channel blocker, flunarizine (10.0 and 40.0 mg/kg), on the hypnotic potency of both a benzodiazepine (BZ)-hypnotic, triazolam (1.0 mg/kg), and a non-BZ hypnotic, zolpidem (20.0 mg/kg), in rats. The polysomnogram was recorded for 6 h after administration of the vehicle solution alone, or after one of the Ca2+ channel blockers, with or without one of the hypnotics. Both Ca2+ channel blockers prolonged the increased total time of non-rapid eye movement (non-REM) sleep induced by either hypnotic. In the case of triazolam, however, the non-REM sleep-enhancing effect induced by nilvadipine was greater than that induced by flunarizine. These findings indicate that the hypnotic action of triazolam is potentiated more strongly by an L-type Ca2+ channel blocker than by a T-type Ca2+ channel blocker.

Animals↗
PubMed1999

[Use of hypnotics in children: description and analysis].

BACKGROUND: Sleep disorders are frequent in pre-school children and in the French population, often leading to the prescription of hypnotics or sedatives. Therefore, this represents an important health problem in this population. PATIENTS AND METHODS: We studied the hypnotic consumption in children, aged between 1 month to 4 years (23 +/- 11.3 months), who complained of insomnia. Parents completed 203 sleep questionnaires including information on the hypnotics consumption of their offspring (112 boys and 91 girls). The questionnaire was also related to the parent's sleep patterns and hypnotics consumption. Seventy percent of the sample had received medication, at least once before the evaluation, and at any age. A positive correlation between hypnotics consumption in mothers and children, particularly boys (odds-ratio = 4.8; 1.1-8.7) was found. CONCLUSION: These data confirm the early exposition to hypnotics of children in the French population, and the existence of a familial pattern of consumption, mostly influenced by the mother. These data should permit the identification of subgroups at risk for early exposition and to encourage non-pharmacologic approaches in the treatment of insomnia in young children.

Age Factors↗
PubMed2004

Attitudes to long-term use of benzodiazepine hypnotics by older people in general practice: findings from interviews with service users and providers.

The aim of this study was to explore beliefs and attitudes about continuing or stopping benzodiazepine hypnotics amongst older patients using such medicines, and amongst their general practitioners. One hundred and ninety two patients aged 65 and over who were long-term users of benzodiazepine hypnotics were recruited from 25 general practices in inner city and suburban London, as were 83 practice staff. The practices had been recruited into a randomised controlled trial of benzodiazepine withdrawal in long-term users. Semi-structured interviews were conducted with patients recruited to the trial, and non-standardized (conversational) interviews with practice staff. Sixty percent of long-term benzodiazepine users had taken their hypnotic for more than 10 years, and one-third for more than 20 years. Beliefs in the efficacy of hypnotics, and self-report of insomnia despite their use, varied according to the willingness to attempt withdrawal. The majority of patients reported no warnings from professionals about adverse effects of using benzodiazepine hypnotics. Half had tried to stop at some time but most attempts had been short-lived. Patients and doctors had distinctly different views of the advantages, disadvantages and risks of stopping benzodiazepine hypnotic use. Both increased patient awareness of the problems of long-term benzodiazepine use and an evidence-based approach to withdrawal efforts in primary care are necessary to reduce the consumption of medication that has little real benefit.

Aged↗
PubMed1990

Chronic use of hypnotics in a family practice--patients' reluctance to stop treatment.

Insomnia is a common symptom in family practice, and hypnotics are frequently prescribed for its treatment. A survey was performed in an urban clinic serving 1900 persons in order to detect the prevalence of this disorder and to reassess the need for hypnotics. Sixty-one patients were identified who were taking prescribed hypnotic drugs, mainly benzodiazepines. All were over the age of 40, and they comprised 8.1% of this age group. Forty-five were chronic users, taking hypnotics for more than 4 months during a 6-month study period. Eighty-nine percent of these chronic users were above 60 years of age. Seventy-seven percent had difficulty initiating sleep and 23% had problems maintaining sleep. Information was given to these patients on the side effects and possible addictive nature of chronic hypnotic use. Different kinds of psychological support were offered as alternatives to drug treatment, but these were refused by all. We conclude that in view of the addiction associated with chronic use and the difficulty of weaning patients off the sleeping pill, there is a place for more careful evaluation and management before hypnotics are prescribed.

Adult↗
PubMed1999

Isobolographic analysis of propofol-thiopental hypnotic interaction in surgical patients.

UNLABELLED: Drugs acting via the same mechanism interact additively, whereas a supraadditive effect can result from an interaction of drugs with different mechanisms of action. Hypnotic midazolam-propofol and midazolam-thiopental interactions are supraadditive. In contrast to midazolam, the mechanisms of actions of propofol and thiopental are quite similar. The aim of this study was to test the hypothesis that similarity in the mechanisms of action of propofol and thiopental results in the additive hypnotic interaction. We studied the hypnotic effects of thiopental, propofol, and their combinations in 150 unpremedicated patients in a randomized, double-blind fashion. The ability to open eyes on command was used as an end point. Dose-response curves for the drugs given separately and in combinations at three different dose ratios between the drugs were determined by using a probit procedure, and the 50% effective dose values were compared by using isobolographic and algebraic (fractional) analysis. The hypnotic propofol-thiopental combination was additive with all dose ratios between components of the combination. The absence of propofol-thiopental synergy, as demonstrated with midazolam-thiopental or propofol-midazolam combinations, suggests that the mechanisms underlying the hypnotic effects of propofol and thiopental, in contrast to the above combinations with midazolam, are very similar and could be identical. IMPLICATIONS: The propofol-thiopental hypnotic interaction is additive.

Adolescent↗
PubMed1990

Pertussis toxin and 4-aminopyridine differentially affect the hypnotic-anesthetic action of dexmedetomidine and pentobarbital.

Dexmedetomidine, a highly selective and potent agonist at alpha-2 adrenoceptors, produces a hypnotic-anesthetic action in rats. The mechanism for this response may involve an inhibitory G-protein and increased conductance through a potassium channel. To investigate this, the effects of pertussis toxin, a specific inactivator of inhibitory G-proteins, and 4-aminopyridine, a blocker of potassium channels, on the hypnotic-anesthetic response to dexmedetomidine were studied in rats. Pertussis toxin and 4-aminopyridine both decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. To preclude the possibility that pertussis toxin and 4-aminopyridine attenuated the hypnotic-anesthetic action of dexmedetomidine via indirect central nervous system excitation, the effects of pertussis toxin and 4-aminopyridine on the hypnotic-anesthetic action of pentobarbital also were assessed. Pentobarbital-induced hypnosis was not attenuated by either treatment. These results suggest that the receptor-effector mechanism for the hypnotic-anesthetic action of dexmedetomidine involves an inhibitory G-protein and increased conductance through a potassium channel.

4-Aminopyridine↗
PubMedDate not supplied

Regular hypnotic drug treatment in a sample of 32,679 Swedes: associations with somatic and mental health, inpatient psychiatric diagnoses and suicide, derived with automated record-linkage.

We studied Swedish survey responders who reported regular treatment with hypnotic drugs, to find associations to perceived health problems, inpatient psychiatric diagnoses, and subsequent suicide. Among 32,679 sampled Swedes, 26,952 (83%) participated, 500 of which (2%) reported regular hypnotic drug treatment. The rate of treatment was higher in women, and increased by age in both sexes. The major findings were high odds of concurrent psychoactive drug treatments, nervous symptoms and insomnia, as well as high rates of circulatory and musculoskeletal conditions in both sexes, with indicators of disability and sleep-disturbing symptoms. During a 15-year period, 35% of the men and 21% of the women who reported regular hypnotic drug treatment had also been admitted to inpatient psychiatric care. Substance abuse was diagnosed in 20% of the men and 4.3% of the women reporting hypnotic drug treatment. In multiple logistic regression models, the highest odds for regular hypnotic drug treatment were incurred by recent/current insomnia, nervous symptoms, and other psychoactive drug treatment. We conclude that therapy was principally given according to some current peer guidelines. Yet, further research is needed into the risk/benefit ratio of sustained hypnotic drug therapy in patients with qualifying somatic and psychiatric disorders to obtain a more uniformly based consensus.

Adolescent↗
PubMed1992

Hypnotics, sleep, and mortality in elderly people.

OBJECTIVE: To re-assess relationships between mortality, hypnotic use, subjective insomnia, and sleep duration. DESIGN: A prospective study examining 5-year mortality among hypnotic drug users and respondents with subjective insomnia identified in a longitudinal study of health, activity, and lifestyle (Nottingham Longitudinal Study of Activity and Ageing). SETTING: General community. PARTICIPANTS: 1042 survey respondents, aged over 65 years, randomly selected from the community and stratified at age 75 years. MAIN OUTCOME MEASURE: Recorded mortality. RESULTS: During the 5-year period, 352 respondents died. The mortality rate was significantly greater among those taking some form of medication for sleep (n = 208) than for those not taking sleep medication (n = 812; chi-square = 4.91, df = 1, P = 0.027). When sleep medication users were categorized as either "hypnotic users" (ie, users of medication with recognized hypnotic or sedative actions) or "other users" (including analgesics and other over-the-counter medicines), only "other users" showed significant excess mortality (chi-square = 7.27, df = 1, P = 0.007). Logistic regression showed that "other users" were 2.5 times more likely to die than "non-users" even when gender, health risk, and usual sleep duration were controlled. There were no significant relationships between mortality and subjective insomnia or reported duration of sleep. CONCLUSIONS: Earlier reported relationships between excess mortality and use of medication for sleep are replicated in this study. Among elderly people, however, this relationship does not derive from the pharmacological characteristics of prescription hypnotics. Rather, it appears that reported self-medication to promote sleep, using a variety of non-sedative products, provides an epidemiological "marker" for a group within which levels of morbidity and mortality are particularly high. Excess mortality associated with very short or long sleep duration was not replicated in this study. Overall, these findings provide little epidemiological support for a wide-spread interaction between benzodiazepine hypnotic use and sleep disordered breathing in old age.

Aged↗
PubMed1968

Dependence on hypnotic drugs in general practice.

Of the patients in an industrial general practice 1.3% required hypnotic drugs regularly. They were predominantly in the older age groups (mean 62.7 years), with an excess of widows. Only 0.02% were severely dependent; the remainder were mildly so, though they had been taking hypnotics for long periods (mean 5.6 years). There were three main original indications for hypnotics-namely, medical (pain), psychiatric, and onset insomnia in anxious personality disorder. One-fifth of the patients first took hypnotics while in hospital. The group as a whole manifested a high degree of abnormal psychological disposition.It is suggested that many patients who take hypnotics regularly may be placebo reactors, and a more critical attitude to hypnotic prescribing is required both in hospital and in general practice.

Adult↗
PubMed1998

Limited anxiolytic-like effects of non-benzodiazepine hypnotics in rodents.

The present experiments compared the anxiolytic-like effects of the benzodiazepine (BZD) hypnotic triazolam with those of four non-BZD hypnotics including one non-selective (zopiclone) and three omega1-BZD selective (zolpidem, zaleplon and SX-3228) receptor ligands, in classical animal models including conflict tests (punished lever pressing and punished drinking tests in rats) and exploratory models (elevated plus-maze test in rats and light/dark choice test in mice), and a recently developed mouse defence test battery (MDTB) which has been validated for the screening of anxiolytic drugs. Results from both conflict procedures showed that zopiclone (0.3-10 mg/kg) produced anxiolytic-like effects comparable to those of triazolam (0.1-3 mg/kg), whereas the selective omega1-BZD receptor hypnotics zolpidem (0.3-3 mg/kg), zaleplon (0.1-3 mg/kg) and SX-3228 (0.1-1 mg/kg) displayed weaker and/or non-specific anxiolytic-like effects. Similarly, in the light/dark test in mice, zolpidem (0.1-1 mg/kg), zaleplon (0.3-10 mg/kg) and SX-3228 (0.03-0.3 mg/kg) showed a reduced potential to produce anxiolytic-like effects as compared to the non-selective omega-BZD receptor hypnotics triazolam (0.03-1 mg/kg) and zopiclone (1-30 mg/kg). In the elevated plus-maze test, zopiclone (1-10 mg/kg), zolpidem (0.1-1 mg/kg), zaleplon (0.3-3 mg/kg) and SX-3228 (0.1-1 mg/kg) displayed anxiolytic-like activity at doses close to those producing behavioural impairment, whereas triazolam (0.03-1 mg/kg) exhibited anxiolytic-like effects over a wide dose range in the absence of decreases in general activity. In the MDTB, zaleplon (0.3-10 mg/kg) decreased all defensive responses, a profile which was similar to that of triazolam (0.03-1 mg/kg), while zopiclone (1-30 mg/kg), zolpidem (0.3-10 mg/kg) and SX-3228 (0.03-1 mg/kg) had fewer effects on defensive behaviours with several effects occurring only at motor-impairing doses. Taken together, these results demonstrate that, although selective omega1-BZD receptor hypnotics display anxiolytic-like activity, the effects are generally weaker than those observed with non-selective omega-BZD receptor selective hypnotics such as triazolam or zopiclone. In particular, the anxiety-reducing potential of the omega1-BZD receptor selective compounds is limited to certain anxiety measures and may be confounded and/or masked by behavioural suppression.

Acetamides↗
PubMed1999

New insights into the mechanism of action of hypnotics.

Between 1987 and 1989, the different protein subunits that make up the receptor for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) were identified. These make up the alpha, beta, gamma and delta families, for each of which exist several subtypes. This receptor is the molecular target of modern hypnotic drugs (i.e. benzodiazepines, zopiclone, zolpidem and zaleplon). In the 10 years that have followed this milestone, significant progress has been made in exploring the molecular mechanisms of hypnotic drug action. Receptor subtype specificity of hypnotics has been explained in terms of differential affinity for receptors containing different alpha subunits, which are expressed in different brain regions. Zolpidem and zaleplon bind preferentially to alpha1-containing receptors, whereas benzodiazepines and zopiclone are aspecific. Different sets of subunits are encoded in contiguous 'cassettes' on the genome, and the transcription of each set appears to be regulated coherently. The predominant GABA(A) receptor composition found in the brain is alpha1beta2gamma2, which are all encoded on human chromosome 5. Targeted gene disruption has provided clues to the physiological functions served by GABA(A) receptors containing different subunits. Receptors containing gamma2 appear to have a vital role in maintaining appropriate central inhibition, beta3-containing receptors may also be important determinants of excitability in certain brain regions, whereas a clear role for alpha5-, alpha6- and gamma3-containing receptors has not yet been established by these techniques. Site-directed mutagenesis has indicated that benzodiazepines bind to a cleft on the GABA(A) receptor surface at the interface between the alpha and gamma subunits. Other drugs (flumazenil, zopiclone, zolpidem) also bind to the a subunit, but interact with amino acids in different binding domains to the benzodiazepines. The molecular mechanism of hypnotic dependence has been explored, and seems to involve downregulation of transcription of the normally prevalent alpha1, beta2 and gamma2 subunits, and the reciprocal upregulation of the expression of rarer subunits. Chronic treatment with hypnotic drugs that may have less dependence potential, such as zopiclone and zolpidem, appears to produce more limited change in GABA(A) receptor subunit expression. These ideas will be important both for designing new hypnotic drugs with a better safety/efficacy profile, and for evaluating more appropriate ways of using the drugs available today.

Animals↗
PubMed2004

Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308].

INTRODUCTION: This randomised, open-label, observational, multicentre, parallel group study assessed the safety and efficacy of analgesia-based sedation using remifentanil in the neuro-intensive care unit. METHODS: Patients aged 18-80 years admitted to the intensive care unit within the previous 24 hours, with acute brain injury or after neurosurgery, intubated, expected to require mechanical ventilation for 1-5 days and requiring daily downward titration of sedation for assessment of neurological function were studied. Patients received one of two treatment regimens. Regimen one consisted of analgesia-based sedation, in which remifentanil (initial rate 9 microg kg(-1) h(-1)) was titrated before the addition of a hypnotic agent (propofol [0.5 mg kg(-1) h(-1)] during days 1-3, midazolam [0.03 mg kg(-1) h(-1)] during days 4 and 5) (n = 84). Regimen two consisted of hypnotic-based sedation: hypnotic agent (propofol days 1-3; midazolam days 4 and 5) and fentanyl (n = 37) or morphine (n = 40) according to routine clinical practice. For each regimen, agents were titrated to achieve optimal sedation (Sedation-Agitation Scale score 1-3) and analgesia (Pain Intensity score 1-2). RESULTS: Overall, between-patient variability around the time of neurological assessment was statistically significantly smaller when using remifentanil (remifentanil 0.44 versus fentanyl 0.86 [P = 0.024] versus morphine 0.98 [P = 0.006]. Overall, mean neurological assessment times were significantly shorter when using remifentanil (remifentanil 0.41 hour versus fentanyl 0.71 hour [P = 0.001] versus morphine 0.82 hour [P < 0.001]). Patients receiving the remifentanil-based regimen were extubated significantly faster than those treated with morphine (1.0 hour versus 1.93 hour, P = 0.001) but there was no difference between remifentanil and fentanyl. Remifentanil was effective, well tolerated and provided comparable haemodynamic stability to that of the hypnotic-based regimen. Over three times as many users rated analgesia-based sedation with remifentanil as very good or excellent in facilitating assessment of neurological function compared with the hypnotic-based regimen. CONCLUSIONS: Analgesia-based sedation with remifentanil permitted significantly faster and more predictable awakening for neurological assessment. Analgesia-based sedation with remifentanil was very effective, well tolerated and had a similar adverse event and haemodynamic profile to those of hypnotic-based regimens when used in critically ill neuro-intensive care unit patients for up to 5 days.

Adjuvants, Anesthesia↗
PubMed1986

Hypnotics. Their place in therapeutics.

Sleep disturbance has become a subject of serious study only over the past few years, but even so there is already an increasing awareness of the nature of insomnia and a greater understanding of the role which hypnotics should play in clinical medicine. An hypnotic may be used to shorten sleep onset when there is difficulty in falling asleep, to reduce nocturnal wakefulness, or to provide an anxiolytic effect during the next day when insomnia is accompanied by a marked element of anxiety. The purpose of an hypnotic is to meet one or more of these clinical problems; to ensure that the patient is given the most useful medication, consideration must be given to duration of activity. This depends on the absorption, distribution and elimination characteristics of the drug. It is now appreciated that the most appropriate use of hypnotics is in the individual with insomnia of recent origin. An hypnotic with the most relevant pharmacokinetic profile should be used for the shortest period of time and then only as required, while low doses will ensure freedom from adverse effects. The place of hypnotics in chronic insomnia remains less certain. Their careful use may well be of benefit, though it must be part of a well defined clinical strategy. Assessment of the patient is essential to identify any specific conditions which would impair sleep.

Acute Disease↗
PubMed1990

Hypnotics in the elderly. What cause for concern?

At any age hypnotic drug use can give rise to 3 major problems: unwanted effects on daytime mood and behaviour associated with drug consumption; rebound effects associated with drug withdrawal; and dependency associated with long term drug use. For 2 reasons elderly hypnotic users are both more vulnerable and more exposed to each of these problems. Firstly, age-related changes in pharmacodynamic and pharmacokinetic processes amplify the behavioural impact of many hypnotics; and secondly, age-related changes in the structure and quality of sleep tend to increase the demand for, and the long term use of, sedative hypnotic compounds in old age. The existence of physical illness, cognitive impairment, or daytime behaviour already compromised by normal aging processes further increases the likelihood of hypnotic drugs detrimentally affecting well-being in later life. These important causes for concern emphasise the need for 2 separate clinical responses: the need for greater circumspection in the choice and use of hypnotic drugs among elderly patients, and the need for a more broadly based clinical approach to the management of sleep problems in old age.

Aged↗
PubMed2006

Factors contributing to sleep disturbance and hypnotic drug use in hemodialysis patients.

OBJECTIVE: Sleep disturbance and the use of hypnotic medications are common in patients on hemodialysis. Factors that contribute to sleep disturbance and the use of hypnotic medications in hemodialysis patients were investigated. METHODS: With the use of a questionnaire-based survey, we examined the prevalence of symptoms that reflect sleep disorders such as insomnia, restless legs syndrome (RLS), and snoring and use of hypnotic medications in 252 hemodialysis patients. RESULTS: The overall prevalence of insomnia was 59.1%, with the prevalence of difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), and early morning awakening (EMA) being 47.6, 24.2, and 28.2%, respectively. Daytime sleepiness and habitual snoring were reported by 42.5 and 33.7%, respectively. The prevalence of routine use of hypnotic drugs was 25.8%. Both RLS and age were significantly associated with insomnia [odds ratio (OR), 3.75; p 0.001, OR, 1.03; p < 0.01]. RLS was a significant factor for DIS, DMS, and EMA (OR, 2.26; p < 0.05, OR, 3.44; p < 0.0005, OR, 4.25; p < 0.0005) and age was a significant factor for DMS and EMA (OR, 1.03; p = 0.053, OR, 1.05; p < 0.005). Both insomnia and snoring were associated with the use of hypnotic drugs (OR, 2.97; p < 0.001, 1.59; p=0.13). CONCLUSION: Both RLS and sleep-disordered breathing may contribute to sleep disturbance in hemodialysis patients. RLS in particular may be an important factor in insomnia, which in turn is likely responsible for the high prevalence of hypnotic drug use in hemodialysis patients.

Adult↗
PubMed2006

Use of hypnotics in Sámi and non-Sámi populations in northern Norway.

OBJECTIVES: Our knowledge of the impact of indigenous culture on drug consumption is scarce. Based on the Sámi Health Study, we compare the use of hypnotics among the Sámi and non-Sámi people, living in the same area at 70 degrees N in northern Norway. STUDY DESIGN: Cross-sectional survey based on a cardiovascular screening, including questionnaires and a clinical examination. METHODS: A total of 16 323 men and women born 1925 - 1967 in counties with a mixed Sámi and non-Sámi population responded to a questionnaire delivered at attendance of a health study. The response rate was 60%. The main analyses were restricted to 12 378 subjects with information on all relevant variables, including ethnicity and use of hypnotics. RESULTS: The prevalence of insomnia and use of hypnotics was significantly lower in the Sámi compared to the non-Sámi population in northern Norway (p < 0.0001). Regardless of ethnicity and age, prevalence of use of hypnotics in women was twice that of men. People who consulted modern, or traditional healers had a higher prevalence of use of hypnotics compared to those who did not. CONCLUSIONS: The stronger the Sámi affiliation, the lower the prevalence of use of hypnotics. In general, insomnia is less frequently stated in the Sámi than in the non-Sámi study population. This may reflect a different attitude to sleep as a phenomenon among the Sámi.

Adult↗
PubMed2003

Co-use of donepezil and hypnotics among Alzheimer's disease patients living in the community.

BACKGROUND: In clinical trials, sleep problems have been identified as side effects of donepezil, an acetylcholinesterase (AChE)-inhibiting medication for the treatment of Alzheimer's disease (AD). Poor sleep quality can exacerbate behavior problems among patients and add to the burden experienced by their caregivers. We examined the relationship between co-use of donepezil and hypnotics in a large sample of persons with AD living in the community. METHOD: This secondary data analysis used cross-sectional subjects from a multiwave, consumer-based survey of AD caregivers conducted in 1997 and 1998. Rates of hypnotic use among users and non-users of donepezil were compared using chi-square analysis for independent samples, and multivariate logistic regression was used to identify significant independent correlates of hypnotic use. RESULTS: A total of 2638 caregivers completed at least 1 study wave. Use of hypnotics was higher in the donepezil subgroup (9.78%) compared with subjects not taking this medication (3.93%). Multivariate analysis demonstrated that donepezil use was independently linked to increased hypnotic use after controlling for the potential confounding effects of disruptive behavior and depressive symptoms (adjusted odds ratio = 3.34, p <.001). CONCLUSION: In this large community sample, donepezil use was statistically linked to increased hypnotic use. Because sleep quality may be a critical issue for persons with AD and their caregivers, more rigorous evaluation of sleep problems linked to AChE-inhibitor treatment is indicated.

Aged↗
PubMed1990

Zopiclone, the third generation hypnotic: a clinical overview.

Effective and safe hypnotics exist especially since the introduction of benzodiazepines (BZD) which appeared to bring major advantages over barbiturates. Ideally a new hypnotic should induce and maintain sleep without producing residual effect during the day and should be devoid of abuse and dependence potential. Zopiclone is a new hypnotic belonging to the cyclopyrrolone chemical class. Its elimination half-life is 5 to 6 h, no accumulation exists upon repeated administration, and its pharmacokinetic profile is not substantially modified in elderly and renal failure patients. Placebo-controlled studies have shown that zopiclone 7.5 mg is an effective hypnotic, and that it can improve all sleep variables in insomniacs. Its effects on sleep stages differ from those observed with BZD hypnotics: REM sleep is substantially unaffected by zopiclone and slow wave sleep is either unaffected or increased. Objective and subjective measurements during the day after bedtime administration of zopiclone, showed lack of residual effects and no residual impairment of cognitive functions. Zopiclone discontinuation is not accompanied by rebound effect and relevant withdrawal symptoms. Specific "craving effect" studies in alcoholics did not show an abuse potential for zopiclone. Side-effects are represented mainly by bitter taste and dry mouth with a minimal incidence of CNS depressant effects. Studies on the effects of zopiclone on respiratory functions failed to show detrimental effects. Efficacy and safety data on zopiclone suggest that this new drug can represent a useful alternative to existing hypnotics.

Azabicyclo Compounds↗