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At least 145 records · Page 8Linked to original sources
PubMed1980

Induction of drug metabolism in the rat by taglutimide, a sedative-hypnotic glutarimide derivative.

Pretreatment with taglutimide significantly decreased the plasma dicoumarol level and shortened the duration of hexobarbital-induced narcosis in rats. Furthermore, taglutimide pretreatment accelerated the in vitro metabolism of dicoumarol, hexobarbital, o-nitrophenyl acetate and procaine, but not of 3,4-benzypyrene, as assayed in the 10,000xg supernatant fraction of rat liver homogenate. No definite increase was observed in liver wet weight, nor in the amount of microsomal and total liver protein in comparison with the control values. No marked differences were found between the effects of short- (4-day) and long-term (17-day) pretreatment on any of the studied parameters. The changes in drug metabolism and liver protein observed after taglutimide pretreatment differed from those observed after pretreatment with either phenobarbital or 3,4-benzypyrene. Taglutimide, like other inducing agents, is lipophilic, but differs from them in not being a substrate of monooxygenases.

Animals↗
PubMed1986

The anti-excitotoxic effects of certain anesthetics, analgesics and sedative-hypnotics.

Various agents were tested for their ability to antagonize the acute excitotoxic action of N-methyl-DL-aspartate (NMA) and kainic acid (KA) on neurons in the in vitro chick embryo retina. The following compounds (in order of descending potencies) were effective in completely blocking the neurotoxic activity of NMA: phencyclidine, ketamine, (+/-)-SKF 10,047, pentazocine, D-aminophosphonovalerate, D-amino-phosphonoheptanoate, D-alpha-aminoadipate, OH-quinoxaline carboxylate, kynurenate, (+/-)-cis-2,3-piperidine dicarboxylate, secobarbital, amobarbital and pentobarbital. The latter 6 agents also protected against KA toxicity but complete protection was observed only from relatively high concentrations. At 20 mM, Mg2+ blocked NMA toxicity but at concentrations up to 30 mM did not block KA toxicity. Compounds that failed to block either NMA or KA toxicity include D- and L-aminophosphonobutyrate, L-glutamic acid diethyl ester, xanthurenate, GABA and taurine. The chick embryo retina is a useful preparation for identifying agents that have either excitotoxic or anti-excitotoxic activity.

Analgesics↗
PubMedDate not supplied

Pretreatment with sedative-hypnotics, but not with nondepolarizing muscle relaxants, attenuates alfentanil-induced muscle rigidity.

STUDY OBJECTIVE: To evaluate and compare the efficacy of various pretreatment agents to attenuate or prevent opioid-induced muscle rigidity using a well-established, previously described clinical protocol. DESIGN: Prospective, controlled, single-blind, partially randomized study. SETTING: Large medical center. PATIENTS: ASA physical status I-III patients undergoing elective surgical procedures of at least 3 hours' duration. INTERVENTIONS: The effect of pretreatment with nondepolarizing muscle relaxants (atracurium 40 micrograms/kg or metocurine 50 micrograms/kg), benzodiazepine agonists (diazepam 5 mg or midazolam 2.5 mg), or thiopental sodium 1 mg/kg on the increased muscle tone produced by alfentanil 175 micrograms/kg was compared with a control group (given no pretreatment). MEASUREMENTS AND MAIN RESULTS: Rigidity was assessed quantitatively by measuring the electromyographic activity of five muscle groups (biceps, intercostals, abdominals, quadriceps, and gastrocnemius). Rigidity also was rated qualitatively by attempts to initiate and maintain mask ventilation, attempts to flex an extremity, and the occurrence of myoclonic movements. Pretreatment with the two nondepolarizing muscle relaxants had no effect on the severe muscle rigidity produced by high-dose alfentanil. Whereas thiopental was only mildly effective, the benzodiazepines midazolam and diazepam significantly attenuated alfentanil rigidity (p < 0.05). CONCLUSION: This study suggests that benzodiazepine pretreatment is frequently, but not always, effective in preventing opioid-induced muscle rigidity.

Abdominal Muscles↗
PubMed2006

Eszopiclone, a nonbenzodiazepine sedative-hypnotic agent for the treatment of transient and chronic insomnia.

OBJECTIVE: This paper reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of the nonbenzodiazepine cyclopyrrolone agent eszopiclone in the management of adult patients with insomnia. METHODS: Recent studies, abstracts, reviews, and consensus statements published in English were identified through searches of MEDLINE (1966-December 2005), International Pharmaceutical Abstracts (1970 December 2005), and PharmaProjects (1990-December 2005) using the search terms eszopiclone, cyclopyrrolone, insomnia, nonbenzodiazepine, and zopiclone enantiomer. Selected information provided by the manufacturer of eszopiclone was included, as were all pertinent clinical trials. RESULTS: Eszopiclone is rapidly absorbed after oral administration, with Tmax achieved within approximately 1 hour and a terminal-phase elimination half-life of approximately 6 hours. Approximately 52% to 59% of a dose is weakly bound to plasma protein. Eszopiclone is extensively metabolized by oxidation and demethylation. In vitro studies have indicated that the cytochrome P450 (CYP) isozymes CYP3A4 and CYP2E1 are involved in the biotransformation of eszopiclone; therefore, drugs that induce or inhibit these CYP isozymes may affect the metabolism of eszopiclone. Eszopiclone is excreted in the urine as racemic zopiclone at <10% of the orally administered dose. Six Phase III clinical trials were identified that evaluated the safety profile and efficacy of eszopiclone, 1 in healthy subjects with transient insomnia and 5 in patients with primary chronic insomnia (3 in younger adults and 2 in the elderly). In the trials in younger adults, eszopiclone significantly improved sleep efficiency, sleep latency, wake time after sleep onset, number of awakenings, number of nights awakened weekly, total sleep time, and quality and depth of sleep compared with placebo (P<0.05). In the trials in elderly patients, who received eszopiclone 2 mg or placebo for 2 weeks, eszopiclone was associated with significantly shorter sleep latency compared with placebo (P<0.004), as well as a significant decrease in the cumulative number of naps (P<0.05). The most commonly reported drug-related, dose-responsive adverse event in clinical trials of eszopiclone 2 and 3 mg was bitter taste (17% and 34%, respectively), followed by dizziness (5% and 7%) and dry mouth (5% and 7%). Somnolence occurred at an incidence of 4% to 9% with both doses. Tolerance or rebound insomnia was not reported. CONCLUSIONS: Eszopiclone represents an effective and well-tolerated option for the treatment of insomnia. In the absence of published studies comparing eszopiclone with similar hypnotic agents (eg, zolpidem, zaleplon, zopiclone), it is not yet possible to evaluate its efficacy relative to other agents used for insomnia.

Azabicyclo Compounds↗
PubMed2005

Long-term use of sedative hypnotics in older patients with insomnia.

BACKGROUND AND PURPOSE: Insomnia is a common problem that increases with age and can last months to years. While substantial data establish the efficacy and safety of short-acting hypnotic therapy for the management of short-term insomnia using benzodiazepines receptor agonists (BzRAs), there are few studies on the continued efficacy and safety of these drugs when used for sustained periods. This paper reports the results of a 1-year open-label extension phases of two randomized, double-blind trials of zaleplon. PATIENTS AND METHODS: In the open-label phase, older patients self-administered zaleplon nightly from 6 to 12 months and were then followed through a 7-day single-blind placebo-controlled run-out period. RESULTS: The safety profile in this population of older adults was similar to that observed in a short-term trial of an equivalent population. The data also suggested that long-term therapy produced and maintained statistically significant improvement in time to persistent sleep onset, duration of sleep and number of nocturnal awakenings (P<0.001 for each variable) for treatment durations of up to 12 months. Discontinuation was not associated with rebound insomnia. CONCLUSION: The open-label trial of long-term hypnotic therapy with zaleplon 5 and 10 mg suggests that they are safe and effective for the treatment of insomnia in older patients. Placebo-controlled, double-blind trials are needed in zaleplon and other BzRAs to confirm these results.

Acetamides↗
PubMed1990

Synthesis and anticonvulsant and sedative-hypnotic activity of 4-(alkylimino)-2,3-dihydro-4H-1-benzopyrans and -benzothiopyrans.

A series of 4-(alkylimino)-5-hydroxy-7-alkyl-2,3-dihydro-4H-1-benzopyrans and -thiopyrans were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2,2-dimethyl-4-[(2-hydroxyalkyl)imino]-5-hydroxy-7-pentyl-2,3- dihydro-4H-1-benzopyrans 19 and 29, the 7-butyl analogue 34, and the corresponding 7-pentyl-4H-1-benzothiopyrans 38 and 39 had the most promising anticonvulsant activity. Synthesis of both enantiomers of 29 and 39 indicated that the R isomers 30 and 40 were the most active and showed very good protection against MES, pentylenetetrazole, and mercaptopropionic acid induced seizures after oral administration in mice. In the Irwin test these compounds showed a generalized depressant activity but at dosages higher than those showing anticonvulsant activity, whereas acute toxicity after oral administration was low (LD50 higher than 400 mg/kg).

Animals↗
PubMedDate not supplied

Retention indices and dual capillary gas chromatography for rapid identification of sedative hypnotic drugs in emergency toxicology.

Recent advances in capillary column technology and gas chromatographic instrumentation allow the reproducible qualitative and semiquantitative determination of drugs in biological samples. A simple, cost-effective, and time saving method is described that utilizes a retention index library for drug identification in emergency toxicology. Samples need not be derivatized because of the inertness of the fused silica capillary system. Dual columns of different polarity are utilized to identify and simultaneously confirm results of biological drug extracts. A summary of the BASIC program used for retention index calculation and library search is included. Results from twenty double blind split specimen analyses are reported.

Body Fluids↗