sodium-oxybate and zopiclone

The analysis of the results obtained in different tests--sleep studies, cortical and hippocampal EEG activity, PGO-R spikes--in rats or in cats allows the characterization of different classes of drugs and to establish the relative efficacy of psychoactive drugs in these models. Moreover, the sequential spectral analysis of cortical EEG recordings in curarized rats allows the assessment of EEG modifications, of the presence of hypersynchronized rhythms, of the induction and duration of drug action, of topographic drug effects and interactions between different agents. Thus, the use of EEG techniques in various animal species allows a better classification and definition of the central action of drugs.

Topics: 5-Hydroxytryptophan; Amantadine; Animals; Antihypertensive Agents; Azabicyclo Compounds; Brain; Cats; Chlormethiazole; Clonidine; Diazepam; Electroencephalography; Flunitrazepam; Guanabenz; Guanfacine; Guanidines; Imidazoles; Male; Nitrazepam; Pentobarbital; Phenylacetates; Piperazines; Piracetam; Rats; Sodium Oxybate; Yohimbine

Date-rape drugs have the potential to be used in drug-facilitated sexual assault, organ theft and property theft. Since they are colorless, tasteless and odorless, victims can drink without noticing, when added to the beverages. These drugs must be detected in time, before they are cleared up from the biofluids. A simultaneous extraction and determination method in urine for GHB, ketamine, norketamine, phenobarbital, thiopental, zolpidem, zopiclone and phenytoin (an anticonvulsant and antiepileptic drug) with LC-MS/MS was developed for the first time with analytically acceptable recoveries and validated. A 4 steps liquid-liquid extraction was applied, using only 1.000mL urine. A new age commercial C18 poroshell column with high column efficiency was used for LC-MS/MS analysis with a fast isocratic elution as 5.5min. A new MS transition were introduced for barbital. 222.7>179.8 with the effect of acetonitrile. Recoveries (%) were between 80.98-99.27 for all analytes, except for GHB which was 71.46. LOD and LOQ values were found in the ranges of 0.59-49.50 and 9.20-80.80ngmL(-1) for all the analytes (except for GHB:3.44 and 6.00μgmL(-1)). HorRat values calculated (between 0.25-1.21), revealed that the inter-day and interanalist precisions (RSD%≤14.54%) acceptable. The simultaneous extraction and determination of these 8 analytes in urine is challenging because of the difficulty arising from the different chemical properties of some. Since the procedure can extract drugs from a wide range of polarity and pKa, it increases the window of detection. Group representatives from barbiturates, z-drugs, ketamine, phenytoin and polar acidic drugs (GHB) have been successfully analyzed in this study with low detection limits. The method is important from the point of determining the combined or single use of these drugs in crimes and finding out the reasons of deaths related to these drugs.

Topics: Azabicyclo Compounds; Barbiturates; Chromatography, High Pressure Liquid; Forensic Sciences; Humans; Hypnotics and Sedatives; Ketamine; Limit of Detection; Linear Models; Liquid-Liquid Extraction; Phenytoin; Piperazines; Pyridines; Rape; Reproducibility of Results; Sodium Oxybate; Zolpidem

REM sleep behavior disorder (RBD) is characterized by loss of the normal muscle atonia during REM sleep associated with disruptive motor activity related to the acting out of dreams. There is frequently injury to the patient or bed partner, and treatment is usually required. Clonazepam has been the first-line therapy for many years, with 2 large case series reporting efficacy with few side effects in the majority of patients. However, long-acting hypnotics in the elderly or those with cognitive impairment can be associated with adverse events especially unacceptable daytime sedation, confusion, and exacerbation of existing sleep apnea.. We reviewed 39 patients with confirmed RBD who were treated within our regional sleep center, assessing both efficacy and side effects of drug therapies.. Adverse effects were reported by 58% of the patients using clonazepam, with 50% either discontinuing the drug or reducing the dose. This prompted us review the side effects of clonazepam in detail and to look for alternative therapies. We report several novel and effective therapies, in particular zopiclone, in a series of patients under long-term follow-up for RBD.. There are alternatives to clonazepam therapy for RBD which can be as effective and may be better tolerated.

Topics: Adjuvants, Anesthesia; Aged; Azabicyclo Compounds; Central Nervous System Depressants; Clonazepam; Cohort Studies; Female; Follow-Up Studies; GABA Modulators; Humans; Hypnotics and Sedatives; Male; Melatonin; Piperazines; Polysomnography; REM Sleep Behavior Disorder; Retrospective Studies; Severity of Illness Index; Sodium Oxybate; Surveys and Questionnaires; United Kingdom