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Abstract Rationale and objectives: Previous studies have shown that insomniacs self-administer hypnotics at high nightly rates. This study determined whether prior experience with different treatment regimens (i.e., instructions and capsule availability) would alter the previously observed high hypnotic self-administration rams. Methods: Sixty-four healthy men and women with (n = 32) and without (n = 32) insomnia, 21-55 years, self administered placebo or triazolam (0.25 mg) after different prior treatment regimens. They received one of three different treatment regimens enforced for 11 nights: a capsule each night, a capsule as needed, or a capsule every third night. On 14 subsequent nights they choose to self-administer a capsule or not, placebo during 1 week and triazolam (0.25 mg) the other (counterbalanced in order). Results: Insomniacs self-administered more capsules than normals and triazolam was self-administered more than placebo. For both groups, treatment regimen had a minimal effect on capsule self-administration. During the treatment phase, triazolam improved self-ratings of sleep relative to placebo. During the choice phase, nightly variations in self-rated sleep predicted self-administration of a capsule on the following night, regardless of whether the capsule was active drug or placebo. Conclusions: The data of this study are consistent with the view that hypnotic self-administration by insomniacs is therapy-seeking behavior and not drug abuse. [ABSTRACT FROM AUTHOR]

Focuses on false recognition in triazolam-induced amnesia. Effect of repetition on false recognition in triazolam-induced amnesia; Interaction between drug condition and number of study presentations; Psychomotor/cognitive performance and participant-rated measures.

Provides information on a study that examined the effects of some drugs with a higher selectivity for the alpha-adrenoceptors on the head-twitch response induced by benzodiazepines, estazolam and triazolam in mice. Methodology of the study; Results and discussion on the study.

This study was designed to examine whether the widely prescribed benzodiazepine hypnotic triazolam has reinforcing effects in moderate social alcohol drinkers, without histories of drug abuse or insomnia, in the context of its use as a hypnotic. Eleven healthy adult volunteers who met criteria for 'good sleepers' participated in a 60-session double-blind choice study which was conducted on an outpatient basis with participants sleeping at home. Twenty three-session sampling/choice tests were conducted sequentially to provide 20 evaluations of the reinforcing effects of 0.25 mg/70 kg triazolam versus placebo, ingested orally 30 min before bedtime. Each three-session test consisted of two sampling sessions, in which participants received exposure to each of the two drug conditions in different colored capsules, followed by one choice session, in which participants were asked to choose one of the two colour-coded capsules for self-administration. Four participants exhibited a significant choice of triazolam, three, a significant choice of placebo (i.e. triazolam avoidance), and four, a random (i.e. non-significant) choice between triazolam and placebo. The reasons provided by participants were consistent with their choices and with the expected effects of triazolam versus placebo. Analyses of post-sleep questionnaires indicated that triazolam did not produce a clinically meaningful improvement in sleep. The finding that triazolam functioned as a reinforcer in participants without insomnia suggests that triazolam has reinforcing effects in some individuals for which hypnotic treatment is not clinically indicated, and that health care professionals must continue to assess the risk/benefit ratio of benzodiazepine hypnotic prescription. [ABSTRACT FROM AUTHOR]

Zolpidem (AMBIEN[sup ®] ), an imidazopyridine, is now the most commonly prescribed hypnotic in the United States. Zolpidem is neuropharmacologically distinct from benzodiazepine hypnotics in that it binds with low affinity to α[sub 5] -containing GABA[sub A] -receptor subtypes. Despite its unique benzodiazepine-receptor binding profile, the results of most of the published studies conducted with humans suggest that the absolute magnitude of impairment produced by zolpidem is comparable to that observed with benzodiazepine hypnotics like triazolam. The present study compared the acute effects of zolpidem (0, 7.5, 15 and 22.5 mg) and triazolam (0, 0.1875, 0.375 and 0.5625 mg) in 10 non-drug-abusing humans using a Digit-Enter-and-Recall task with varying delay intervals (0, 10 and 20 s). To more fully characterize the behavioral effects of zolpidem and triazolam, several other performance tasks and subject-rated drug-effect questionnaires were included. Zolpidem and triazolam impaired performance on the Digit-Enter-and-Recall task as a function of dose under all delay intervals. However, the dose-related effects of the drugs interacted differentially with the delay interval such that zolpidem produced significantly less impairment than triazolam following the longest delay (i.e., 20 s). Zolpidem and triazolam produced comparable dose-related impairment on the digit symbol substitution test (DSST), circular lights task, and picture recall/recognition task. Zolpidem and triazolam generally produced qualitatively and quantitatively similar subject-rated drug effects, although some between-drug differences were observed. Consistent with the pharmacokinetics of these drugs, the effects of zolpidem peaked sooner and were shorter in duration than those observed with triazolam. The results of this experiment suggest that zolpidem may have less potential than triazolam to impair recall, which may be due to differences between these compounds in terms of their benzodiazepine-receptor binding profile. The results of the present study are also concordant with previous studies that found that drugs that act at the GABA[sub A] -receptor complex can be differentiated based on their interaction with the delay interval on a Digit-Enter-and-Recall task. Copyright © 2001 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract Rationale: Triazolam is a high-efficacy benzodiazepine (BZ) agonist, which might be hypothesized to engender highly pharmacologically specific discriminative stimulus (DS) effects and distinguish among BZ agonists with different intrinsic efficacy. Objectives: The pharmacological specificity of the triazolam stimulus was determined by examining the effects of conventional and atypical BZ agonists, and other ligands active at the gamma-aminobutyric acid[sub A] (GABA[sub A]) receptor complex. Receptor mechanisms underlying the DS effects of triazolam were examined further using the BZ receptor antagonist flumazenil. Methods and results: Squirrel monkeys were trained to discriminate triazolam (0.03 mg/kg, i.v.) from vehicle under a fixed-ratio 10 (FR 10) schedule of food reinforcement. While the BZ agonists midazolam, diazepam, and lorazepam substituted fully for triazolam, chlordiazepoxide, oxazepam and nordiazepam produced only partial substitution, suggesting these latter compounds may have reduced intrinsic efficacy. The BZ/alpha[sub 1]-preferring agonist zolpidem substituted fully for triazolam, and potencies for triazolam-like effects of BZ agonists were significantly correlated with potencies for their zolpidem-like effects (Rowlett et al. 1999). Flumazenil antagonized the DS effects of triazolam, but the slope of the Schild plot was significantly different from unity, suggesting multiple receptors may be involved in the DS effects of triazolam. Conclusions: BZ agonists can be distinguished on the basis of substitution for triazolam and... [ABSTRACT FROM AUTHOR]

The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0·25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0·25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0·25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0·25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0·25 mg) produced increases in total sleep time (25 min) and decreases in latency to persistent sleep at a dose of 0·25 mg. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Investigates the acute effects of the orally-administered benzodiazepine, triazolam, on false recognition. Significant dose-related reductions in false recognition rates to nonstudied words associatively related to studied words seen in amnesic patients receiving triazolam; Evidence that false recognition relies on normal memory mechanisms impaired in benzodiazepine-induced amnesia.

Focuses on the epidemiologic findings on the treatment of insomnia in the United States. Use of nonbenzodiazepine hypnotics as a pharmacological treatment; Effects of acute and repeated doses of zolpidem on sleep; Comparison between the outcome of zolpidem and triazolam on memory functions and psychomotor performance.

Objective: Grapefruit juice inhibits CYP3A4-mediated metabolism of several drugs during first pass. In this study, the effect of grapefruit juice dose on the extent of grapefruit juice–triazolam interaction was investigated. Methods: In a randomised, four-phase, crossover study, 12 healthy volunteers received 0.25 mg triazolam with water, with 200 ml normal-strength or double-strength grapefruit juice or, on the third day of multiple-dose [three times daily (t.i.d.)] administration of double-strength grapefruit juice. Timed blood samples were collected up to 23 h after dosing, and the effects of triazolam were measured with four psychomotor tests up to 10 h after dosing. Results: The area under the plasma triazolam concentration–time curve (AUC0–∞) was increased by 53% (P < 0.01), 49% (P < 0.01) and 143% (P < 0.001) by a single dose of normal-strength, a single dose of double-strength and multiple-dose administration of double-strength grapefruit juice, respectively. The peak plasma concentration (Cmax) of triazolam was increased by about 40% by a single dose of normal-strength grapefruit juice (P < 0.01) and multiple-dose grapefruit juice (P < 0.01) and by 25% by a single dose of double-strength grapefruit juice (P < 0.05). The elimination half-life (t1/2) of triazolam was prolonged by 54% during the multiple-dose grapefruit juice phase (P < 0.001). A significant increase in the pharmacodynamic effects of triazolam was seen during the multiple-dose grapefruit juice phase in the digit symbol substitution test (DSST, P < 0.05), in subjective overall drug effect (P < 0.05) and in subjective drowsiness (P < 0.05). Conclusions: Even one glass of grapefruit juice increases plasma triazolam concentrations, but repeated consumption of grapefruit juice produces a significantly greater increase in triazolam concentrations than one glass of juice. Thet1/2 of triazolam is prolonged by repeated consumption of grapefruit juice, probably due to inhibition of hepatic CYP3A4 activity. [ABSTRACT FROM AUTHOR]

Presents information on a study which evaluated the differential impairment of Triazolam and Zolpidem clearance by Ritonavir. Methodology of the study; Results and discussion on the study.

Purpose. To quantitatively predict the in vivo interaction betweentriazolam and erythromycin, which involves mechanism-basedinhibition of CYP3A4, from in vitro studies using human liver microsomes(HLM) and recombinant human CYP3A4 (REC). Methods. HLM or REC was preincubated with erythromycin in thepresence of NADPH and then triazolam was added. α- and 4-hydroxy(OH) triazolam were quantified after a 3 min incubation and the kineticparameters for enzyme inactivation (kinact and K′) were obtained.Drug-drug interaction in vivo was predicted based on aphysiologically-based pharmacokinetic (PBPK) model, using triazolam anderythromycin pharmacokinetic parameters obtained from the literature and kineticparameters for the enzyme inactivation obtained in the in vitro studies. Results. Whichever enzyme was used, triazolam metabolism was notinhibited without preincubation, even if the erythromycin concentrationwas increased. The degree of inhibition depended on preincubationtime and erythromycin concentration. The values obtained for kapp) were obtained.Drug-drug interaction in vivo was predicted based on aphysiologically-based pharmacokinetic (PBPK) model, using triazolam anderythromycin pharmacokinetic parameters obtained from the literature and kineticparameters for the enzyme inactivation obtained in the in vitro studies. Results. Whichever enzyme was used, triazolam metabolism was notinhibited without preincubation, even if the erythromycin concentrationwas increased. The degree of inhibition depended on preincubationtime and erythromycin concentration. The values obtained for kinactand K′ app were 0.062 min−1 and 15.9 μM (α-OH, HLM), 0.055 min−1 and 18.9 μM (4-OH, REC). Based on the kineticparameters obtained using HLM and REC, the AUCpo of triazolamwas predicted to increase 2.0- and 2.6-fold, respectively, followingoral administration of erythromycin (333 mg t.i.d. for 3 days), whichagreed well with the reported data. Conclusions. In vivo interaction between triazolam and erythromycinwas successfully predicted from in vitro data based on a PBPK modelinvolving a mechanism-based inhibition of CYP3A4. [ABSTRACT FROM AUTHOR]−1 and 19.1 μM (α-OH, REC),and 0.097 min−1 and 18.9 μM (4-OH, REC). Based on the kineticparameters obtained using HLM and REC, the AUCpo of triazolamwas predicted to increase 2.0- and 2.6-fold, respectively, followingoral administration of erythromycin (333 mg t.i.d. for 3 days), whichagreed well with the reported data. Conclusions. In vivo interaction between triazolam and erythromycinwas successfully predicted from in vitro data based on a PBPK modelinvolving a mechanism-based inhibition of CYP3A4. [ABSTRACT FROM AUTHOR]

Recent estimates indicate a 10% prevalence of chronic insomnia in the adult population of the United States. with an associated annual cost of more than $90 billion. Since its approval in 1982 for use in the treatment of insomnia, an estimated 11 billion prescriptions for Halcion(R) (triazolam) have been filled worldwide. Concerns about the salary of Halcion began to emerge when a Dutch psychiatrist reported a possible link between the drug and a syndrome that included depression, amnesia, hallucinations, and anxiety. Since that time. the United Kingdom. Brazil. Argentina. Norway. and Denmark removed Halcion from the market. and the manufacturer. Upjohn, withdrew Halcion from the market in The Netherlands. Other countries, including the United States and Canada. modified the labeling to reduce the recommended dose and duration of treatment and to heighten awareness regarding possible side effects affecting behavior and cognition. The labeling changes raised questions regarding the hypnotic effectiveness of these lower doses of Halcion, Based on a 1996 U.S. Food and Drug Administration (FDA) task force report, the Institute of Medicine (IOM) of the National Academy of Sciences assessed the adequacy, quality, and overall confidence in the data on the effectiveness and safety of Halcion at different doses and durations, including those specified in the current product labeling, This article provides a summary of the IOM report titled "Halcion: An Independent Assessment of Safety and Efficacy Data" and a more detailed overview of the statistical analysis that led to the committee's conclusions. [ABSTRACT FROM AUTHOR]

Presents a study on systematic treatment of hamsters with triazolam (TRZ) or novel wheel (NW) access. How the expected effect of TRZ injected at CT 6 h on the average phase advance was eliminated; Materials and methods; Behavioral analysis; Discussion of the results of the study.

Objective: The efficacy and tolerability of zaleplon 5mg and 10mg, a selective benzodiazepine subtype A receptor agonist, was evaluated during 14-day administration in a double-blind, placebo-controlled design, with triazolam included as an active comparator. Patients and Methods: Polysomnographic data, subjective reports, performance measures, and clinical assessments were made for 132 primary insomniacs, aged 18 to 60 years, during three baseline, 14 drug, and two discontinuation nights. Results: Polysomnographic data indicated that both doses of zaleplon shortened latency to persistent sleep relative to placebo, during early drug administration. By the end of the administration period the difference was no longer statistically significant, principally due to improvement in the placebo group. No effect on total sleep time or measures of awakenings was seen with either zaleplon dose. Triazolam increased total sleep time and reduced latency to persistent sleep compared with placebo on early drug nights, but not at the end of the 2-week administration. In general, subjective data were consistent with polysomnography findings. Clinical evaluations indicated that zaleplon was well tolerated and without residual effects or discontinuation effects. Adverse effects were infrequent, mild and no more common with zaleplon than with placebo. Conclusion: At the doses evaluated, zaleplon appeared to have hypnotic properties consistent with its pharmacokinetic profile, and a low likelihood of undesired effects. [ABSTRACT FROM AUTHOR]

The antagonistic effects of zolpidem 10 mg on withdrawal symptoms caused by abrupt or gradual discontinuation (half-dose over 4 nights) of triazolam 0·25 mg in patients with chronic insomnia, who had been receiving regular treatment for over one month, were assessed in a randomized, double-blind, placebo-controlled clinical trial in general practice. Eighty-four patients were enrolled, mostly women (67·9%), with a mean age of 54·3±11·0 years. Twenty-one different general practitioners were solicitated for the recruitment. The subjects were randomized into four groups, and all received triazolam 0·25 mg during the run-in phase from day 1 (D1) to day 3 (D3). The following treatments were given from D4 to D7: triazolam 0·125 mg+zolpidem 10 mg (Group 1); zolpidem 10 mg (Group 2); placebo (Group 3); or triazolam 0·125 mg+placebo (Group 4). Groups 1 and 2 received zolpidem 10 mg from D7 to D24, while Groups 3 and 4 received placebo. Finally, all four groups received placebo (blind withdrawal phase) from D25 to D28. The following assessment criteria were used: clinical global impression (CGI) scale completed by the practitioner; patient questionnaire based on routine sleep criteria, wakefulness and daytime alertness. Secondary criteria were sleep diaries and visual analogue scales. Study drop-outs were reported and explained. The effectiveness/tolerance ratio was found to be statistically significant using the CGI (p <0·007) in favour of zolpidem 10 mg. There was no significant difference in patients subjective assessment between the groups except for nightmares (p <0·04) less frequent in patients receiving zolpidem. Zolpidem was found to be more effective than placebo at D21 (CGI) according to sleep diaries; the zolpidem group showed a statistically significant difference as compared to the three other concerning four sleep parameters: number of awakenings, anxiety, sleep duration, energy. Drop-out rates were significantly lower in the zolpidem group than in other ones (p <0·01). Abrupt and gradual triazolam withdrawal over 4 nights induced withdrawal symptoms. Equally no specific phenomena were observed at the end of the trial during the blind withdrawal phase. This study shows that zolpidem 10 mg improves sleep quality and reduces withdrawal symptoms after abrupt or gradual discontinuation of triazolam 0·25 mg in chronic patients with chronic insomnia. Copyright © 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Zopiclone is a cyclopyrrolone hypnosedative that is chemically unrelated to the benzodiazepines but nevertheless potentiates γ-aminobutyric acid-mediated neuronal inhibition, and has demonstrated proven efficacy and good tolerability in the treatment of insomnia over 15 years of use. Zopiclone is indicated for short term use, and should not be prescribed for more than 4 weeks. This review compares the efficacy of zopiclone with that of a number of commonly used short-, medium- and long-acting benzodiazepines. Zopiclone at dosages of 7.5 mg/day has demonstrated efficacy equivalent and in some cases greater to that of flurazepam 30 mg/day, nitrazepam 5 mg/day, flunitrazepam 1 to 2 mg/day, temazepam 20 mg/day, triazolam 0.125 to 0.5 mg/day and mid-azolam 15 mg/day. Zopiclone-treated patients reported themselves to be less impaired by daytime sedation than patients treated with the medium- and long-acting hypnosedatives flurazepam, nitrazepam and flunitrazepam. Zopiclone and temazepam showed similar effects on daytime behaviour while zopiclone appeared to have somwhat better effects on daytime well-being than the short-acting triazolam and midazolam. There has been no clinical comparison with the frequently used medium-acting benzodiazepines lormetazepam and brotizolam and the imidazopyridine hypnosedative zolpidem. Data from clinical trials, pooled analyses and postmarketing surveillance including over 30 000 patients showed that with the exception of bitter taste (reported by <10% of zopiclone recipients), the tolerability profile of zopiclone is similar to that of placebo. Clinical trials found no evidence for significant rebound insomnia and indicated that the risk of withdrawal reactions with therapeutic doses of zopiclone is very low. In addition, to date, dependency appears very low, although abuse potential should be considered following a history of addiction or psychiatric illness. Evaluation of the accumulated evidence from over 2.5 billion... [ABSTRACT FROM AUTHOR]

This paper presents a case study in the production and interpretation of regulatory science, focusing on the conflicting British and American clinical risk assessments of triazolam (Halcion) — the most controversial sleeping pill in the world. The regulation of triazolam is shown to be more permissive in the USA than in the UK. Six principal socio-political factors are put forward to explain this: differential regulatory trust; regulators' socio-technical data selections; medico-scientific disciplinary influences; organizational and professional interests; conflicts of interest of expert advisers; and the growth of the neo-liberal regulatory state. The risk assessments of both the British and American regulatory agencies are shown to be complacent relative to technical standards which the agencies themselves later accepted. It is suggested that, when the interests of pharmaceutical manufacturers and patients diverge, regulatory assessments are crucially affected by whether regulators are predisposed to award the benefit of the scientific doubts to the manufacturers or patients, and by the balance of such predispositions both within and between regulatory institutions of scientific expertise. The triazolam case indicates that the amount of trust placed in the pharmaceutical industry by the British and American regulatory systems may hamper detection of flaws in manufacturers' medical data in a timely manner and, as a consequence, compromise patients' interests. Some policy implications for drug regulation are sketched. [ABSTRACT FROM AUTHOR]

Abstract Rationale: The imidazopyridine hypnotic zolpidem may produce less memory and cognitive impairment than classic benzodiazepines, due to its relatively low binding affinity for the benzodiazepine receptor subtypes found in areas of the brain which are involved in learning and memory. Objectives: The study was designed to compare the acute effects of single oral doses of zolpidem (5, 10, 20 mg/70 kg) and the benzodiazepine hypnotic triazolam (0.125, 0.25, and 0.5 mg/70 kg) on specific memory and attentional processes. Methods: Drug effects on memory for target (i.e., focal) information and contextual information (i.e., peripheral details surrounding a target stimulus presentation) were evaluated using a source monitoring paradigm, and drug effects on selective attention mechanisms were evaluated using a negative priming paradigm, in 18 healthy volunteers in a double-blind, placebo-controlled, crossover design. Results: Triazolam and zolpidem produced strikingly similar dose-related effects on memory for target information. Both triazolam and zolpidem impaired subjects' ability to remember whether a word stimulus had been presented to them on the computer screen or whether they had been asked to generate the stimulus based on an antonym cue (memory for the origin of a stimulus, which is one type of contextual information). The results suggested that triazolam, but not zolpidem, impaired memory for the screen location of picture stimuli (spatial contextual information). Although both triazolam and zolpidem increased overall reaction time in the negative priming task, only triazolam increased the magnitude of negative priming relative to placebo. Conclusions: The observed differences between triazolam and zolpidem have implications for the cognitive and pharmacological mechanisms underlying drug-induced deficits in specific memory... [ABSTRACT FROM AUTHOR]

Abstract Abuse liability and acute subjective and psychomotor effects of flunitrazepam were assessed in ten methadone-maintained males with history of benzodiazepine and alcohol use, who voluntarily participated in a double-blind, controlled, cross-over, randomized clinical trial. There were six experimental sessions in which a single oral dose of flunitrazepam 1, 2, and 4 mg; triazolam 0.5 and 0.75 mg; and placebo was given. Evaluations included physiological measures; psychomotor performance tasks (simple reaction time, Digit Symbol Substitution Test, balance task, Maddox-wing device); and self-administered subjective effects questionnaires [Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS), a series of visual analog scales (VAS)]. All drugs but flunitrazepam 1 mg caused an impairment of psychomotor tasks. Effects were more evident with the highest doses of both drugs. Only flunitrazepam 4 mg produced a significant decrease in balance time. Triazolam 0.75 mg induced increases in sedation measured by ARCI-PCAG, depression in POMS, and VAS-drowsiness scores. Flunitrazepam 4 mg caused euphoria-related effects as measured by increases in ARCI-MBG and "high" scores in the VAS. Our findings of flunitrazepam-induced euphoria in methadone-maintained subjects together with epidemiological evidence of flunitrazepam abuse by opioid dependents, suggest that it may be included in the group of benzodiazepines with a relatively high abuse potential. [ABSTRACT FROM AUTHOR]

The effects of triazolam on cognitive function and vigilance on the morning following a nocturnal administration were investigated using event-related potentials (ERP) measurement and a sleep latency test (SLT). We previously reported a significant reducing effect on target N1 amplitude on the morning following triazolam administration, suggesting a residual effect of triazolam. In order to demonstrate, which aspect of cognitive function alteration caused the reducing effect on N1 amplitude, we added the ignore condition for ERP measurement, which enabled us to separate mismatch negativity (MMN) from other subcomponents overlapping N1. As a result, MMN was attenuated and sleep latency was shortened on the morning following triazolam administration. Two possibilities were suggested for the mechanism of MMN attenuation. One is GABAergic activation caused by the residual effect of triazolam per se, and the other is the lowered vigilance level demonstrated in the SLT. Further studies are necessary to determine whether this alteration in physiological bases underlying mismatch detection is specific to triazolam and/or other benzodiazepines or related to nonspecific vigilance level. [ABSTRACT FROM AUTHOR]

This study conceptualizes organizational public relations as attempts to construct ideological world view. Three aspects of ideological world view—distortion, legitimation, and terrain of struggle—are elaborated and then grounded in a case study of the public relations practices of The Upjohn Company, a pharmaceutical manufacturer and researcher, during the Halcion® (sleeping pill) crisis in the 1980s. The case study reveals how such practices helped create a supportive scientific world view for Halcion, which may have contributed to the product' s steady growth in sales and profits during the decade, despite intense media scrutiny and criticism and the restrictive actions of health authorities in some countries. [ABSTRACT FROM AUTHOR]

Triazolam has shown promise as a sedative agent for use in pediatric dentistry. However, the efficacy of triazolam has not been previously examined in a placebo-controlled study. The present clinical trial used a two-group, randomized, double-blind study design to compare the efficacy of oral triazolam with that of a placebo. The primary hypothesis tested was that triazolam would reduce negative behaviors of pediatric dental patients compared with a placebo. A secondary hypothesis was that triazolam would increase the efficiency of dental treatment by reducing the need for time-consuming behavior management by the pediatric dentist. The subjects were 54 3- to 5-year-old children, randomly assigned to the drug and placebo groups. The active drug, 0.03 mg/kg triazolam (Halcion®), or lactose placebo was given orally 30 min before dental treatment. Behavior management techniques commonly used in pediatric dentistry were used during dental treatment. A single pediatric dentist provided all of the dental treatment. The procedure included an inferior block anesthesia and careful attention to anesthesia effectiveness. All sessions were videotaped and the tapes coded for child and dentist behaviors by an independent observer. There were no statistically significant differences between the groups with respect to completion of dental treatment. There were no significant differences found in either the total time or the percent of time that the subjects exhibited disruptive movements, verbal or non-verbal distress. The total use of time in the dental chair was slightly higher in the placebo than in the drug group due to more time spent preparing the child. Contrary to preliminary reports in the literature, this investigation found little or no improvement in child behavior when triazolam was used as a sedative compared with a placebo. However, triazolam did shorten the length of dental treatment, primarily by reducing dentist time in preparing the child for the dental procedure (e.g., establishing rapport and shaping behavior). [ABSTRACT FROM AUTHOR]

The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a mAChR antagonist, in oxygenated Krebs-Ringer solution at 37°C. During incubation, time-resolved imaging of [11C]NMPB binding in the slices was constructed on the storage phosphor screens. Addition of triazolam (1 μM) plus muscimol (30 μM), a GABAA receptor agonist, to the incubation mixture decreased the specific binding of [11C]NMPB. Ro15-1788, a BZ receptor antagonist, prevented this effect, indicating that the effect was exerted through the GABAA/BZ receptor complex. These results demonstrated that stimulation of the GABAA/BZ receptor lowers the affinity of the mAChR for its ligand, which may underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such effect in the P2-fraction instead implies that the integrity of the neuronal cells and/or their environment is prerequisite for the modulation of mAChR by GABAA/BZ stimulation. [ABSTRACT FROM AUTHOR]

This paper offers an analysis of the events surrounding the suspension of the licence for the widely used sleeping tablet Halcion (triazolam) by the British Licensing Authority in October 1991. It is argued that these events highlight a growing crisis in modern medical treatments and in the social relations of health care. This is illustrated by focusing on four elements which have contributed to Halcion becoming a public issue and to its suspension and subsequent banning, namely the claims-making activities of medical experts, the development of legal challenges to medicine, the role of the media and the response of the state. [ABSTRACT FROM AUTHOR]

Examines the effects of triazolam in performance and sleep in a model of transient insomnia. Link of increased duration and continuity of sleep with dose of triazolam; Reduction of the speed of performing several psychomotor tasks and impaired memory consolidation after drug administration; Lack of effect of drugs on accuracy of performance.

Equipotent doses of lormetazepam, triazolam and flunitrazepam were studied for their effect on K-complexes, sleep spindles and rapid eye movements (REM). Receptor affinity was used as the criterion for equipotency. This showed that triazolam, lormetazepam and flunitrazepam display a ratio to each other of 1:2:4. However, it was found that lormetazepam caused only slight changes in the three neurophysiological parameters despite being given at twice the dose considered to be equipotent. In contrast, triazolam and flunitrazepam produced a great reduction in the number of K-complexes, a marked increase in steep spindles and a substantial reduction of REM activity; both substances suppressed the first REM period, and flunitrazepam even suppressed the second in some cases. The influence of all three benzodiazepines on the dissociation of K-complexes and sleep spindles is, however, equal; epochs with either K-complexes or sleep spindles are favoured compared to epochs with both K-complexes and sleep spindles. The general reduction in the number of K-complexes and increase in sleep spindles can be interpreted as a sleep-protective effect. However, the parameter for dose-finding should be REM suppression, since this has the most profound adverse effect on the cyclical structure of sleep-now considered to be the most reliable indicator of a balanced sleep pattern. [ABSTRACT FROM AUTHOR]

Day-time sleep and residual effects of quazepam 15mg. triazolam 0·5mg. flunitrazepam 1 mg, and placebo, alone and in combination with ethanol, were studied using a randomized, double-blind, crossover, single-dose design. Eight healthy volunteers, four male and four female, aged 19-24 years. received each medication in the morning alter a 'normal' sleep at home the preceding night. Quazepam and triazolam decreased the sleep onset when compared to placebo. The combination with ethanol did not change these findings. Quazepam and placebo showed less residual effects than triazolam and flunitrazepam at 4 hours after drug intake: in combination with ethanol at 4 and 6 hours. No significant differences in mood were found between the different 'treatments', except with regard to alertness for quazepam and placebo compared to flunitrazepam. alone and in combination with ethanol, all at 4 hours. The combination drug/ethanol showed an increase in Cmax of the former and a delay in Tmax when compared to drug alone. The study indicated few clinically useful correlations between clinical effect and plasma concentration. [ABSTRACT FROM AUTHOR]

The effects of zopiclone 7-5 and 15 mg triazolam 0-25 and 0-5 mg, flunitrazepam 1 and 2mg, ethanol and placebo on performance, mood and sleep onset latency after partial sleep deprivation, were compared in a randomized, double-blind, crossover, single-dose study. Sixteen healthy volunteers of both sexes, aged 21-31 years. were included in the study. The overall assessment of the total psychological measurement indicated that zopiclone 7-5 mg, triazolam 0-25 mg and ethanol (C max=0-40 parts per thousand) did not affect the daytime performance of an unacceptable degree even when given late at night. The findings for flunitrazepam I mg were not so uniform, but also seemed acceptable. Zopiclone 15mg, triazolam 0-5mg and flunitrazepam 2mg were rated as not acceptable alternatives. No significant differences were shown concerning mood. The overall assessment for sleep onset latency and subjective aleterness indicated that zopiclone 7-5mg and triazolam 0-25mg had a more appropriate profile than the other drugs and doses rested. [ABSTRACT FROM AUTHOR]

A case of abuse of triazolam, a short-acting benzodiazepine, was experienced. A 35-year-old male, with a tendency to mixed drug dependence with nitrazepam, etc., and a background of neurotic anxiety and insomnia, started self-administration of triazolam. Application of triazolam was frequent. with large doses up to a maximum of 80 mg/day (320 times the recommended daily dose of 250 micrograms). In addition to psychic dependence, occurrence of withdrawal symptoms confirmed formation of physical dependence, which was also supported by EEC together with the appearance of various autonomic and psychic symptoms. Even though triazolam is known to be comparatively sale, this case confirms that it can induce physical dependence upon frequent administration of a large amount, together with psychic dependence, and therefore care must be taken with regard to dosage. In particular, self-administration of the drug should be strictly controlled. [ABSTRACT FROM AUTHOR]

Rebound insomnia is a transient intense worsening of sleep usually appearing within 3 days from the abrupt discontinuation of benzodiazepines (mainly short-acting), following long term use and abuse of these hypnotics. Zolpidem is an imidazopyridine, that binds selectively at ω1-receptor subtypes within the GABAA receptor supramolecular complex. It has a rapid onset of action and short-elimination half-life; it reduces the latency of sleep and prolongs the duration of sleep in patients with insomnia, without any major effects on sleep stages and rebound effects upon discontinuation. The present multicentre trial (three Italian centres) was aimed at assessing the symptoms/signs of rebound insomnia after discontinuation of either zolpidem or triazolam. A double-blind, randomized, parallel group trial of 20-day duration was carried out in 22 patients suffering from either transient insomnia, or short-term (situational stress) insomnia, or patients who were poor sleepers. The trial consisted of three periods: a 3-day run-in period with placebo, a 14-day active treatment period (zolpidem 10 mg od or triazolam 0.25 mg od), a 3-day withdrawal period with placebo. There were statistically significant [p=0.0064 for Total Sleep Time (TST) and p=0.0051 for Sleep Efficiency (SE%)] differences between triazolam- and zolpidem-treated patients during the first withdrawal night versus baseline: TST decreased to 34.5 rain after triazolam but increased to 43.8 rain after zolpidvm, and a similar evolution was shown on SE% (a decrease of 6.3 per cent after triazolam and an increase of 9.9 per cent after zolpidem). Also the Wake-time After Sleep Onset (WASO) showed a statistically significantly (p=0.0083) different pattern, during the first withdrawal night, remaining decreased after zolpidem (37.5 min) but suddenly increasing after triazolam (17.3 min). Also the subjective time to fall asleep changed with a statistically significant difference (p=0.042), being increased after triazolam (8.6 min) and decreased after zolpidem (20.8 min). The results of the study demonstrate the presence of clear rebound insomnia after triazolam discontinuation, whereas such a drawback is absent with zolpidem. This allows the abrupt discontinuation of zolpidem without any need for a tapering procedure and without any risk of pharmacological dependence. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate possible pharmacokinetic and pharmacodynamic interactions between buspirone administered repeatedly and triazolam given acutely. Ten healthy volunteers participated in the study and received 0.25 mg of triazolam orally after a one-week pretreatment with either placebo or buspirone 5 mg t.i.d. the study design was double-blind and crossover, the subjects receiving two times triazolam after the random administration of buspirone or placebo, each treatment period being separated by a washout period of 1 week. Plasma triazolam concentrations were measured by a radio-receptor assays using ³H-flunitrazepam as radioligand. Psychomotor effects of triazolam were measured through subjective self ratings scales and various cognitive tests exploring concentration, memory and psychomotor skills. Overall, the results of the study failed to demonstrate any significant difference in triazolam subjective effects as well as in triazolam plasma concentrations after a one-week pretreatment with either placebo or buspirone 15 mg daily. They do suggest that clinically relevant interactions are unlikely to appear when buspirone at moderate dosage is co-prescribed with acute doses of triazolam, though these data not exclude the possibility of pharmacokinetic interactions between the two drugs. Finally our data also suggest the need for more specific studies in order to demonstrate a possible improvement of psychomotor functions after buspirone administration. [ABSTRACT FROM AUTHOR]