Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “HYPNOTICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed2003

Encapsulation and release of the hypnotic agent zolpidem from biodegradable polymer microparticles containing hydroxypropyl-beta-cyclodextrin.

The goal of this study was to design a prolonged release system of the hypnotic agent zolpidem (ZP) useful for the treatment of insomnia. In this work, ZP alone or in the presence of HP-beta-CD was encapsulated in microparticles constituted by poly(DL-lactide) (PDLLA) and poly(DL-lactide-co-glycolide) (PLGA) and the drug release from these systems was evaluated. ZP alone-loaded microparticles were prepared by the classical O/W emulsion-solvent evaporation method. Conversely, ZP/HP-beta-CD containing microparticles were prepared by the W/O/W emulsion-solvent evaporation method following two different procedures (i.e. A and B). Following procedure A, the previously produced ZP/HP-beta-CD solid complex was added to the water phase of primary emulsion. In the procedure B, HP-beta-CD was added to the aqueous phase and ZP to the organic phase. The resulting microparticles were characterized about morphology, size, encapsulation efficiency and release rates. FT-IR, X-ray, and DSC results suggest the drug is in an essentially amorphous state within the microparticles. The release profiles of ZP from microparticles were in general biphasic, being characterized by an initial burst effect and a subsequent slow ZP release. It resulted that co-encapsulating ZP with or without HP-beta-CD in PDLLA and PLGA the drug release from the corresponding microparticles was protracted. Moreover, in a preliminary pharmacological screening, the ataxic activity in rats was investigated and it was found that intragastric administration of the ZP/HP-beta-CD/PLGA microparticles prepared according to procedure B produced the same ataxic induction time as the one induced by the currently used formulation Stilnox. Interestingly moreover, there was a longer ataxic lasting and a lower intensity of ataxia produced by the ZP/HP-beta-CD/PLGA-B-formulation already after 60 min following the administration. However, a need for further pharmacokinetic and pharmacodynamic studies resulted to fully evaluate the utility of this last formulation for the sustained delivery of ZP.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2004

Voltammetric behavior and quantification of the sedative-hypnotic drug chlordiazepoxide in bulk form, pharmaceutical formulation and human serum at a mercury electrode.

Chlordiazepoxide is a sedative-hypnotic drug widely employed as a transquilizer and anti-depressant. Its electrochemical behavior in Britton-Robinson (B-R) buffers of pH 2-11 at a mercury electrode has been investigated using dc-polarography, cyclic voltammetry and controlled-potential coulometry. Polarograms of the drug in B-R buffers of pH 2-10 exhibited three 2-electron waves, while at pH>10, only a single 4-electron wave was observed. The first, second, and third waves in buffers of pH 10) may be due to the reduction of both the N-oxide and C=N centers in a one step. The shift of the E(1/2,) values to more negative potentials upon the increase of pH indicated the involvement of protons in the electrode reaction and that the proton-transfer reaction precedes the electrode process proper. The estimated data indicated that, one proton and two electrons are participated in the rate-determining step of each of the reduced centers. The general sequence of chlordiazepoxide reduction processes via each of its reactant centers may be expressed as: H(+), e, e, H(+)((fast)).Based on the interfacial adsorptive character of the drug onto the mercury electrode, a validated direct square-wave adsorptive cathodic stripping (SWAdCS) voltammetric procedure has been described for the trace determination of the drug in bulk form, tablets and human serum. The procedure did not require sample pretreatment or time-consuming extraction or evaporation steps prior to the assay of the drug. The optimized operational conditions of the proposed procedure have been found to be: accumulation potential E(acc.)=-0.9 V, accumulation time t(acc.)=30s, pulse-amplitude=50 mV, scan increment=10 mV and frequency=120 Hz. The proposed procedure is much more simple, fast, sensitive, costly low and achieved much more lower limits of detection (LOD) (4.4 x 10(-10)M and 6.6 x 10(-10)M) and limits of quantitation (LOQ) (1.5 x 10(-9)M and 2.2 x 10(-9)M), respectively in pharmaceutical formulation and spiked human serum, compared to previously reported methods.

Chemistry, Pharmaceutical↗
PubMed2005

Melatonin as a hypnotic: pro.

In diurnal species, nocturnal melatonin secretion coincides with the habitual hours of sleep, in contrast to nocturnal animals which are at the peak of their activity while producing melatonin. Studies in humans, diurnal non-human primates, birds and fish show that melatonin treatment can facilitate sleep initiation during the daytime or improve altered overnight sleep. Behaviorally, the sleep-promoting effects of melatonin are distinctly different from those of common hypnotics and are not associated with alterations in sleep architecture. The effects of melatonin on sleep are mediated via specific melatonin receptors and physiologic doses of the hormone, those inducing circulating levels under 200 pg/ml, are sufficient to promote sleep in diurnal species. Aging reduces responsiveness to melatonin treatment and this correlates with reduced functional potency of melatonin receptors. Since melatonin receptors are present in different tissues and organs and involved in multiple physiologic functions, using physiologically relevant doses (0.1-0.3 mg, orally) and time of administration (at bedtime) is recommended, in order to avoid known and unknown side effects of melatonin treatment.

Adult↗
PubMed2005

Anxiolytic-hypnotic drug use associated with trust, social participation, and the miniaturization of community: a multilevel analysis.

The concept of social capital has gained wide interest in public health research in recent years. However, we suggest a concept that was introduced and developed by Fukuyama, named "miniaturization of community", as an alternative to that of social capital. The concept of miniaturization of community emphasizes that a high level of social participation can be accompanied by a low level of trust, both at the individual and at the community level, which may in turn result in social disorder and lack of social cohesion. When society becomes more disordered, people may tend to feel more insecure and anxious. Use of anxiolytic-hypnotic drugs (AHDs) could under such circumstances be a coping strategy. In this study, we first wanted to investigate whether the contextual component of the miniaturization of community concept (i.e. area high social participation and low trust) is associated with individual AHD use, over and above individual characteristics. Secondly, we aimed to study whether people living in the same municipality share a similar probability of AHD use, after adjusting for individual characteristics, and if so, how large this contextual phenomenon is. We used data on 20,319 women and 17,850 men aged 18-79 years from 58 municipalities in six regions in central Sweden, who participated in the Life & Health year 2000 postal survey. We applied multilevel logistic regression analysis with individuals at the first level and areas at the second level. Our results suggest that living in an area with a high level of miniaturization of community seems to be associated with individual AHD use, beyond people's individual characteristics including their own level of social participation and trust. The concept of miniaturization of community may be an extension of the classic concept of social capital and may increase our understanding of contextual effects on health.

Adolescent↗
PubMed2000

Receptor subtype and dose dependence of dexmedetomidine-induced accumulation of [14C]glutamine in astrocytes suggests glial involvement in its hypnotic-sedative and anesthetic-sparing effects.

Dexmedetomidine, a selective alpha(2)-adrenergic agonist, increases accumulation of [14C]glutamine and its labeled metabolites in primary cultures of mouse astrocytes. The concentration dependence is biphasic and identical to that previously described for dexmedetomidine's effect on free cytosolic calcium concentration ([Ca(2+)](i)) in astrocytes, and both effects are exerted on the alpha(2A) subtype of the alpha(2) receptor, suggesting a Ca(2+)-mediated effect. The concentration corresponding to the most potent effect is similar to that with which dexmedetomidine exerts its anesthetic-sparing activity in vivo, and the second peak corresponds to its hypnotic-sedative effect. It is suggested that both effects may be caused by decreased glutamatergic neurotransmission, secondary to reduced availability of glutamine as a glutamate precursor in glutamatergic neurons.

Anesthetics↗
PubMed1999

The nitric oxide-cGMP system of the locus coeruleus and the hypnotic action of alpha-2 adrenergic agonists.

Dexmedetomidine (Dex), a potent, selective alpha-2 adrenergic agonist, injected bilaterally directly into the locus coeruleus (LC), 7 microgram/LC, or ip, 100 microgram/kg, produced a maximum decrease in LC cGMP (-38 and -46%, respectively). Atipamezole, a selective alpha-2 adrenergic antagonist, given into the LC, 10 microgram/LC, prevented the decrease in LC cGMP induced by Dex, given i.p. or into the LC. Dex produced a loss of righting reflex in about 80% of the animals, an effect which was prevented by pretreatment with atipamezole. The nitric oxide synthase antagonist L-Name injected bilaterally into the LC, 20 microgram/LC, produced by itself a maximum decrease in LC cGMP of 54.5%. Dex, 100 microgram/kg, ip, given after L-Name, did not further decrease LC cGMP. L-Name, by itself, did not produce a loss of righting reflex, while 6 out of 9 rats pretreated with L-Name lost their righting reflex in response to Dex. A role of the nitric oxide-cGMP system of the LC in the modulation of the hypnotic effect of alpha-2 adrenergic agonists remains uncertain.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1977

Routine analysis of barbiturates and some other hypnotic drugs in the blood plasma as an aid to the diagnosis of acute poisoning.

A gas-liquid chromatographic method has been devised whereby both the qualitative and the quantitative analysis of a number of hypnotic drugs in the blood may be accomplished simultaneously. Small (50-mul) plasma aliquots are required. The technique is rapid and will detect 2 mg/l concentrations of these compounds. The barbiturates glutethimide, methaqualone, and meprobamate are the principal drugs covered by the scheme. After overdose the concentrations that occur in man are at, or above, this minimum level of detection.

Barbiturates↗
PubMedDate not supplied

Independence of sleep EEG responses to GABAergic hypnotics: biological implications.

GABAergic hypnotics are known to depress non-rapid eye movement delta and rapid eye movements and to stimulate non-rapid eye movement sigma (spindles) and beta EEG. This study addressed the question of whether the magnitudes of these effects are significantly correlated. Data were from a study in 16 normal subjects whose sleep was recorded for five nights under placebo and for three nights each under zolpidem (10 mg), triazolam (0.25 mg) and temazepam (30 mg). EEG was analyzed with both period-amplitude and power spectral (FFT) analysis. The magnitudes of the EEG and eye movement density responses were not significantly correlated for any of the three drugs. It is therefore unlikely that sleep responses to GABAergic drugs can be explained by the common cellular action (increased chloride conductance) of these drugs. We suggest that the sleep EEG responses are manifestations of complex (but consistent) interactions of excitation and inhibition in large brain systems although certain aspects of these responses (e.g. the different time courses of delta vs sigma and eye movement responses) may reflect molecular adaptations. A separate observation in this study was the strong traitlike characteristics of the sleep variables studied. These variables were highly correlated across nights of baseline sleep; in addition, individual differences in baseline sleep were significantly retained on the third night of temazepam administration.

Adult↗
PubMed1985

Pharmacological effects of sedative-hypnotics, narcotic analgesics, and alcohol during sleep.

This article briefly reviews the well known effects of sedative-hypnotics, alcohol and narcotics on sleep. These drugs also have respiratory depressant effects, and the limited information about their effects on sleep-related breathing disturbances is reviewed. They exacerbate obstructive sleep apnea syndrome and have moderate to minimal effects on occasional apnea or hypopnea, but do not induce breathing disturbances de novo.

Adult↗
PubMed1986

Barbiturate and nonbarbiturate sedative hypnotic intoxication in children.

This article reviews the pharmacology, toxicology, and treatment of both barbiturate and nonbarbiturate sedative hypnotic overdose. Although poisoning with these agents has declined over recent years, intoxication with them can still result in a life-threatening situation requiring immediate assessment and treatment.

Anti-Anxiety Agents↗
PubMed1998

Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human performance and memory.

Zolpidem (Zol), an omega1-agonist, acts via GABA(A) receptors but may differ qualitatively from diazepam (Dz) and other benzodiazepines (BZDs). We conducted a placebo-controlled, randomized, double-blind, and crossover study to compare the psychomotor and cognitive effects of 15 mg Zol with those of 15 mg Dz, 30 mg oxazepam (Ox), 7.5 mg zopiclone (Zop), and ethanol (EOH; 0.65 + 0.35 g x kg(-1)) given to 12 subjects at 1-week intervals. Psychomotor tests (symbol digit substitution, simulated driving, flicker fusion, body sway) were done before and 1, 3.5, and 5 h after intake; immediate and delayed memory were measured between 1.5 and 3.5 h. The plasma concentrations of drugs were measured by gas chromatography and by radioreceptor assay (RRA). The mean values of EOH in blood at 1.5, 4, and 5.5 h were 0.82, 0.88, and 0.6 g x l(-1), and the mean values of RRA-assayed plasma Dz were 470, 330, and 210 microg x l(-1), respectively. The corresponding values of other hypnosedatives, in Dz equivalents (microg x l(-1)), were 550, 750, and 330 for Ox; 350, 270, and 70 for Zol; and 160, 210, and 70 for Zop. The standard RRA graph for Zol was significantly flatter than those for other hypnotics. Zol impaired coordinative, reactive, and cognitive skills at 1 and 3.5 h more clearly than the other agents did, the most sensitive performance (tracking) still being impaired by Zol at 5 h. Dz and Zop were less active than Zol objectively; subjective sedation after Dz and Zol was stronger than after Zop. Compared to placebo, all active agents tended to impair learning and memory, their decremental effects, in declining order, being Zol, Dz > EOH, Ox > Zop. During the delay, Dz and Zol caused similar losses of material that had been learned. When separating "true" delayed memory from immediate memory (attention important), Dz and Zol had equieffects on delayed memory and were more detrimental than Zop. When contrasting that against the impaired psychomotor performances, it is possible that 15 mg Zol impairs memory relatively less than 15 mg Dz does.

Adult↗
PubMed1998

Inhibition of cytochrome P450-dependent monooxygenases by an alkaloid fraction from Helietta apiculata markedly potentiate the hypnotic action of pentobarbital.

Crude alkaloid fraction (CAF) isolated from the leaves of Helietta apiculata showed the presence of furoquinolines. The extract was investigated to determine if it can enhance the sensitivity of the central nervous system (CNS) to the hypnotic action of pentobarbital. Administration of CAF to mice in a dose range of 300-500 mg/kg prior to an injection of pentobarbital (40 mg/kg, i.p.) was associated with a statistically significant decrease of sleep latency and prolongation of pentobarbital-induced sleeping time. Pretreatment of rats with the same alkaloid extract (150 mg/kg, i.p. for 4 days) prior to administration of pentobarbital (40 mg/kg, i.p.) caused not only significant reduction of the levels of microsomal proteins, total cytochrome P450 enzymes and a decrease of aminopyrin-N-demethylation and 3,4-benz(a)pyrene hydroxylation but also changed the pattern of cytochrome P450. It is concluded that the CAF isolated from H. apiculata can potentiate the CNS depressant effect of pentobarbital due to alteration of barbiturate metabolism through inhibition, mainly, of cytochrome P450-dependent enzymes.

Animals↗
PubMed1999

Anxiolytic and hypnotic use in 376 psychiatric inpatients. GERMED Neuropsychotropics Group.

This objectives of this study were three-fold: retrospectively evaluate anxiolytic/hypnotic consumption by psychiatric inpatients, identify the risk factors of prolonged intakes, and prospectively measure the impact of hospitalisation on the use of those drugs. Three hundred and seventy-six patients hospitalised in 11 psychiatric departments in the Paris region were studied using a structured interview for the anxiolytic/hypnotic treatments, DSM-III-R criteria, GHQ-12, HAD, Spiegel's questionnaire, COVI's anxiety scale and the CGI. Eighty-five per cent of the patients had taken one anxiolytic/hypnotic or more in the 3 months preceding hospitalisation. Hospitalisation induced little change in anxiolytic/hypnotic use: dosage frequency increased from 77% to 84% between the week preceding hospitalisation and that preceding discharge; 26% of consumers were taking at least two anxiolytics or two hypnotics in the first period vs. 23% in the second. The absence of withdrawal during hospitalisation was related to the high age and a diagnosis of depression rather than schizophrenia, to the existence of continuous intake over the 3 months preceding hospitalisation and to higher drug doses during the 7 days preceding hospitalisation. Prescription of treatment at the end of hospitalisation in previously non-user subjects was related to a higher HAD anxiety score at discharge.

Anti-Anxiety Agents↗
PubMed1997

Evaluation of zolpidem, triazolam, and placebo as hypnotic drugs the night before surgery.

STUDY OBJECTIVE: To compare the hypnotic effects of a bedtime dose of zolpidem, triazolam, and placebo. DESIGN: "Double-blind, randomized, placebo- and active-controlled, parallel-group" trial. SETTING: Six Canadian hospitals. PATIENTS: 357 patients (aged 19 to 71 years) hospitalized the night before a surgical procedure. INTERVENTIONS: At bedtime, each patient received either zolpidem 10 mg, triazolam 0.25 mg, or placebo, and was allowed to sleep for a maximum of 8 hours. MEASUREMENTS: Outcome measures were subjective in nature and included a morning questionnaire, visual analog scales, and observation forms by study personnel. All continuous variables were analyzed by analysis of variance. All categorical data were compared using the Cochran-Mantel-Haenszel (CMH) test, and the percentage of patients asleep was compared using a CMH chi-square analysis. When significant overall treatment effects were observed, pairwise comparisons were undertaken. Compared with the placebo group, the following parameters were significantly (p < 0.001) different in the zolpidem and triazolam groups: sleep latency was shorter, total sleep time was longer, patients fell asleep more easily, and the number of patients awake 2 hours after drug administration was lower. There were no differences between any groups in next-morning somnolence or ability to concentrate. Both drugs were well tolerated, with adverse event incidence rates nearly identical to placebo. CONCLUSIONS: In patients suffering from transient insomnia, a single dose of zolpidem 10 mg was as effective as triazolam 0.25 mg, and both were more effective than placebo and were well tolerated.

Adult↗
PubMed1997

Comparison of isoflurane and midazolam as hypnotic supplementation to moderately high-dose fentanyl during coronary artery bypass grafting: effects on systemic hemodynamics and early postoperative recovery profile.

OBJECTIVE: The aim of this study was to compare isoflurane and midazolam as hypnotic adjuncts to moderately high-dose fentanyl during coronary artery bypass grafting (CABG) with regard to perioperative hemodynamics and early postoperative recovery profile. DESIGN: Prospective open randomized clinical trial. SETTING: Single university-affiliated medical center. PARTICIPANTS: Thirty patients scheduled for elective primary CABG were randomly divided into two groups receiving either isoflurane or midazolam as adjuncts to 50 micrograms/kg of fentanyl. INTERVENTION: Anesthesia was induced with intravenous fentanyl, 10 micrograms/kg, and midazolam, 0.1 mg/kg, and maintained with either isoflurane, 0.6% or midazolam, 0.1 mg/kg/hour, in intravenous infusion. Before the sternotomy, all patients received 30 micrograms/kg of fentanyl. Midazolam and isoflurane were stopped at the start of cardiopulmonary bypass (CPB). At rewarming, all patients received fentanyl, 5 to 10 micrograms/kg, and either isoflurane, 0.6%, or midazolam, at a reduced rate of 0.05 mg/kg/h. Changes in systolic blood pressure of more than 20% from baseline were first treated with vasoactive drugs. Hypertension was corrected with ketanserin, 10 to 20 mg; hypotension with ephedrine, 5 mg. For a mean blood pressure of less than 50 mmHg during CPB phenylephrine, 0.25 to 0.5 mg, was administered. When hypotension persisted despite a vasopressor, the administration of midazolam or isoflurane was stopped. Postoperatively, the patients were mechanically ventilated overnight and sedated with intermittent doses of fentanyl, 0.15 mg, and midazolam, 5 mg. MEASUREMENTS AND MAIN RESULTS: Routine five-lead electrocardiogram (ECG) and invasive hemodynamic monitoring using a pulmonary artery catheter were performed. The mean dose of fentanyl was 3.9 mg in the midazolam group versus 3.6 mg in the isoflurane group. There were no significant perioperative differences between groups in cardiac output, filling, or pulmonary artery pressures. Systolic blood pressure from the initial incision to CPB was lower in the isoflurane group compared with the midazolam group. During this interval, ketanserin was required in nine patients from the midazolam group at a mean dose of 26 mg, compared with only one patient in the isoflurane group. During and after CPB, there was no difference in ketanserin and in vasopressive/inotropic agent requirements. Temporary cessation of midazolam was required in four patients, for a mean of 34 minutes; whereas isoflurane was stopped in 10 patients for 36 minutes, mostly in the post-CPB period. Time to awakening and to extubation in the midazolam group (217 minutes and 19.5 hours) and the isoflurane group (193 minutes and 18.2 hours) were comparable. Between intensive care unit (ICU) admission and extubation, the patients in the midazolam group received 0.89 mg of fentanyl and 36.5 mg of midazolam compared with 0.98 mg of fentanyl and 36.2 mg of midazolam in the isoflurane group. There was a tendency for a higher postoperative pulmonary shunt and more severely impaired oxygenation in the isoflurane group. CONCLUSION: Midazolam supplementation to fentanyl required more frequent antihypertensive escape during the pre-CPB period than isoflurane. However, more frequent cessation of isoflurane caused by hypotension was needed in the post-CPB period. No difference in awakening and ICU discharge was found.

Aged↗
PubMed2002

Do high or low doses of anxiolytics and hypnotics affect mismatch negativity in schizophrenic subjects? An EEG and MEG study.

OBJECTIVE: Many studies have demonstrated mismatch negativity (MMN) attenuation in schizophrenia. Recently, investigators have shown that GABAergic inhibitory neurons may regulate MMN generation. Considering that a substantial proportion of schizophrenic patients receive anxiolytics and hypnotics that have affinity to GABA(A) receptors to reduce their comorbid symptoms of anxiety and sleep disturbances, we need to assess whether anxiolytics/hypnotics might affect their MMN generation. The aim of this study is to assess the possibility that high or low doses of anxiolytics/hypnotics received by schizophrenic subjects affect their mismatch negativity (MMN), using event-related potentials (ERPs) and magnetoencephalography (MEG). METHODS: Twenty-three and 16 patients with schizophrenia participated in the ERP and MEG studies, respectively. Three types of MMN (MMN in response to a duration change of pure-tone stimuli, within-category vowel change (Japanese vowel /a/ with short versus long duration), and across-category vowel change (vowel /a/ versus /o/)) were recorded. RESULTS: High or low doses of benzodiazepine had no significant effects on MMN amplitude/magnetic MMN power, topography/laterality, or latency under any conditions of the ERP or MEG study. CONCLUSIONS: These results suggest that chronic administration of anxiolytics/hypnotics does not significantly affect MMN in schizophrenia.

Acoustic Stimulation↗
PubMed1975

Synthesis of an active hydroxylated glutethimide metabolite and some related analogs with sedative-hypnotic and anticonvulsant properties.

Two synthetic pathways are described for the preparation of 4-hydroxy-2-ethyl-2-phenylglutarimide (2), an active hydroxylated metabolite of glutethimide (1). Fourteen other glutethimide analogs were also synthesized and tested for biological activity. Most of the analogs exhibited sedative-hypnotic properties and compound 2 possessed the greatest activity compared to the parent drug. 4-Amino-2-ethyl-2-phenylglutarimide and 4-hydroxy-2-ethyl-2-phenylglutaconimide (13) exhibited the greatest potential as anticonvulsant agents. The structure-activity relationships of the series are discussed.

Animals↗
PubMed1999

Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem.

1. The benzodiazepines are among the most frequently prescribed of all drugs and have been used for their anxiolytic, anticonvulsant, and sedative/hypnotic properties. Since absorption rates, volumes of distribution, and elimination rates differ greatly among the benzodiazepine derivatives, each benzodiazepine has a unique plasma concentration curve. Although the time to peak plasma levels provides a rough guide, it is not equivalent to the time to clinical onset of effect. The importance of alpha and beta half-lives in the actions of benzodiazepines is discussed. 2. The role of cytochrome P450 isozymes in the metabolism of benzodiazepines and in potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs is discussed. 3. Buspirone, an anxiolytic with minimal sedative effects, undergoes extensive metabolism, with hydroxylation and dealkylation being the major pathways. Pharmacokinetic interactions of buspirone with other coadministered drugs seem to be minimal. 4. Zopiclone and zolpidem are used primarily as hypnotics. Both are extensively metabolized; N-demethylation, N-oxidation, and decarboxylation of zopiclone occur, and zolpidem undergoes oxidation of methyl groups and hydroxylation of a position on the imidazolepyridine ring system. Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics. Metabolic drug-drug interactions have been reported with zopiclone and erythromycin, trimipramine, and carbamazepine. Reports to date indicate minimal interactions of zolpidem with coadministered drugs; however, it has been reported to affect the Cmax and clearance of chlorpromazepine and to decrease metabolism of the antiviral agent ritonavin. Since CYP3A4 has been reported to play an important role in metabolism of zolpidem, possible interactions with drugs which are substrates and/or inhibitors of that CYP isozyme should be considered.

Anti-Anxiety Agents↗