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Sedative hypnotics.

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Hypnotics and Sedatives↗
PubMed1992

Classical genetic analyses of responses to sedative-hypnotic drugs in crosses derived from long-sleep and short-sleep mice.

A classical (Mendelian) genetic analysis of responses to eight sedative-hypnotic compounds (ethanol, urethane, trifluoroethanol, chloral hydrate, barbital, paraldehyde, methyprylon, pentobarbital) was conducted in crosses derived from mouse lines that were selectively bred for differential duration of anesthesia following ethanol. The sleep-time responses of these mice, the long-sleep (LS) and short-sleep (SS) mouse lines, as well as the F1, F2 and backcross (F1 x LS, F1 x SS) generations were measured. Generally, differences in responses among the generations were greater for water soluble compounds than were differences for more lipid soluble compounds. Also, the inheritance of responses to water soluble compounds could be explained primarily by additive effects of alleles while the inheritance patterns for more lipid soluble compounds were more complex. Genetic correlation with ethanol response decreased with increasing lipophilicity. These results suggest that the selection of the LS-SS mouse lines was specific for water soluble anesthetic agents. Because several of these agents are known to act at GABA receptors, examination of the interactions of compounds which differ in lipid solubility at GABA receptors from LS and SS mice may prove useful in elucidating the mechanism of the anesthetic actions of ethanol and other drugs.

Alcohol Drinking↗
PubMed1990

The use of sedative-hypnotic drugs in a university teaching hospital.

We reviewed the charts of 476 patients admitted to a university teaching hospital to determine whether sedative-hypnotic drugs (SHDs) were being used excessively and to examine the use of SHDs as hypnotics. The frequency of medical and surgical indications for barbiturates and benzodiazepines or other minor tranquillizers as well as the use of such drugs were compared among different groups of patients and specialty wards. Of the patients 29% had a regular order and 40% had a PRN order; only 77% of the PRN orders were administered. A total of 215 patients (45%) received an SHD during their hospital stay, and 160 (34%) received the drug as a hypnotic. Medical indications accounted for 49% of the regular orders but only 2% of the PRN orders; moreover, 89% of all the PRN orders were for insomnia. On average, patients receiving SHDs as hypnotics were older (p less than 0.05) and stayed longer in hospital (p less than 0.01) than those who did not; however, no patient on the geriatric or pediatric ward received an SHD as a hypnotic during the hospital stay. The differences in use between patient groups may have been influenced by orientation of ward staff. Physicians should review their rationale for prescribing hypnotics and avoid routine orders on admission.

Adult↗
PubMed1979

Pharmacological properties of taglutimide, a new sedative-hypnotic drug.

2-[Bicyclo(2,2,1)heptane-2-endo-3-endo-dicarboximido]-glutarimide (taglutimide, K-2004) proved to be a new sedative-hypnotic drug which did not produce any toxic effects when administered orally to mice even at a very high dosage. Central-nervous depression was demonstrated by a reduction in spontaneous motor activity, potentiation of the central-depressant effect of pentobarbital, antagonism of the central-stimulant effect of amphetamine after oral administration and by narcotic activity after i.v. administration of the drug. Furthermore, oral administration of taglutimide potentiated the analgesic action of morphine without being effective on its own. Only weak potentiation of chlorpromazine-induced catalepsy, but not of reserpine-induced catalepsy was observed after taglutimide pretreatment. The drug influenced neither motor co-ordination nor the toxicity of ethanol. Taglutimide exhibited no anticonvulsant activity with respect to maximum electroshock or strychnine-induced seizures. No effect on heart rate or blood pressure was demonstrable after taglutimide treatment in conscious dogs.

Animals↗
PubMed1982

Out-patient detoxification of patients addicted to sedative-hypnotics and anxiolytics.

Due to the risk of seizures and other potentially life threatening complications, it has been accepted practice to detoxify patients addicted to sedative-hypnotics or minor tranquilizers in an in-patient setting. Using the procedures for patient selection and management described below, we have been able to detoxify as out-patients approximately two-thirds of 69 patients who were found to be in need of detoxification. Out-patients experienced no serious complications during or immediately following detoxification and were not significantly less likely than in-patients to complete treatment. We present here some guidelines which will assist practitioners in identifying patients who are appropriate for out-patient detoxification and describe approaches to patient management that have proven effective.

Ambulatory Care↗
PubMed1982

Species differences in the disposition and metabolism of 1-methyl-3-(3-pyridyl)-5-(2-hydroxy-methylphenyl)-1H-1,2,4-triazole, a potential sedative-hypnotic compound.

1. Disposition and metabolism of 1-methyl-3-(3-pyridyl)-5-(2-hydroxy-methylphenyl)-1H-1,2,4-triazole, a new sedative-hypnotic, were studied in rats (i.v. and p.o.), cats (i.v.) and human volunteers (p.o.) with 14C-labelled drug. 2. In rat and man, the compound is well absorbed, extensively metabolized, and excreted mostly through the kidney; it has short plasma half-lives, 0.6 h in rat, 0.9 h in man, and 1.9 h in cat. 3. In rat and man metabolism involves N-oxidation of the pyridine ring (Metabolite I), and in cat oxidation of the hydroxymethyl group (Metabolite II). Four other conjugated metabolites (III-VI) isolated from rat urine and bile, and from urine of cats and man, have been characterized. 4. The unchanged compound, but not its metabolites, crosses the blood-brain barrier in rat and cat. 5. The species differences in the disposition and metabolism of the compound are consistent with previous pharmacological data indicating a greater and more prolonged effect in cat.

Adult↗
PubMed2002

Anticonvulsant and sedative-hypnotic activities of N-substituted isatin semicarbazones.

A series of N-methyl/acetyl, 5-(un)-substituted isatin-3-semicarbazones were screened for anticonvulsant and sedative-hypnotic activities. The results revealed that protection was obtained in all the screens i.e., MES, scPTZ, and scSTY. Compounds 2, 4, 6, 10 but not 1 and 3 showed low neurotoxicity when compared to clinically used drugs. Compounds 5, 7, 8 and 9 were completely non-toxic. Compound 6 showed good activity in the rat oral MES screen. Among all the compounds, 3 and 6 emerged as the most active compounds as indicated by the protection they exhibit in MES, scSTY, and scPTZ screens. All the compounds showed significant sedativehypnotic activity.

Animals↗
PubMed1990

Identification and differentiation of barbiturates, other sedative-hypnotics and their metabolites in urine integrated in a general screening procedure using computerized gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric procedure is described for the identification and differentiation of sedative-hypnotics and their metabolites in urine. The following 24 barbiturates and thirteen other hypnotics could be detected: acecarbromal, allobarbital, amobarbital, aprobarbital, barbital, brallobarbital, bromisoval, (sec)butabarbital, butalbital, butobarbital, carbromal, clomethiazole, crotylbarbital, cyclobarbital, cyclopentobarbital, diethylallylacetamide, dipropylbarbital, glutethimide, guaifenesin, ethinamate, heptabarbital, hexobarbital, meprobamate, methaqualone, metharbital, methohexital, methylphenobarbital, methyprylone, pentobarbital, phenobarbital, propallylonal, pyrithyldione, secobarbital, thiobutabarbital, thiopental, vinbarbital and vinylbital. The procedure presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs detecting over 300 drugs and over 1000 of their metabolites. It includes cleavage of conjugates by acid hydrolysis, isolation by liquid-liquid extraction, derivatization by acetylation, separation by capillary gas chromatography, and identification by computerized mass spectrometry. Using mass chromatography with the selected ions m/z 83, 117, 141, 167, 169, 207, 221 and 235, the presence of barbiturates, other hypnotics and/or their metabolites was indicated. The identity of positive signals in the reconstructed mass chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The sample preparation, mass chromatograms, reference mass spectra and gas chromatographic retention indices are documented.

Acetylation↗