indiplon and zopiclone

Topics: Animals; Azabicyclo Compounds; Benzodiazepines; Diphenhydramine; Drug Design; Fluorobenzenes; GABA-A Receptor Agonists; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Indenes; Orexin Receptors; Phenols; Piperazines; Pyridines; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Serotonin 5-HT2 Receptor Antagonists; Sleep Initiation and Maintenance Disorders; Thiophenes; Zolpidem

Insomnia is a prevalent problem in late life. Sleep problems in the elderly are often mistakenly considered a normal part of aging. Insomnia, the most common sleep disorder, is a subjective report of insufficient or nonrestorative sleep despite adequate opportunity to sleep. Despite the fact that more than 50% of elderly people have insomnia, it is typically undertreated, and nonpharmacologic interventions are underused by health care practitioners. This article will review the causes of insomnia in the elderly, the approach to patient evaluation, and the nonpharmacologic and pharmacologic treatment of insomnia.

Topics: Acetamides; Aged; Aging; Antidepressive Agents; Azabicyclo Compounds; Behavior Therapy; Benzodiazepines; Humans; Hypnotics and Sedatives; Nonprescription Drugs; Piperazines; Pyridines; Pyrimidines; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Sleep; Sleep Initiation and Maintenance Disorders; Sleep, REM; Thiophenes; Trazodone; Zolpidem

To assess the effects of post-bedtime dosing with indiplon on next-day function in adults and the elderly.. Two randomized, double-blind, placebo-controlled crossover studies were conducted in two groups of healthy volunteers: an adult study (18-45 years) and an elderly study (65-80 years). In adults, a single post-bedtime dose of indiplon 10 mg and 20 mg was compared to placebo, with zolpidem 10 mg and zopiclone 7.5 mg included as controls. In the elderly, a single post-bedtime dose of indiplon 5 mg and 10 mg was compared to placebo, with zopiclone 3.75 mg included as a control. Next-day residual effects were evaluated in the morning at 4 and 6 h post-dose in adults, and 4, 6, and 8 h in the elderly, by a Visual Analog Scale of sleepiness (VAS-sleepiness), Digit Symbol Substitution Test (DSST), and the Symbol Copying Test (SCT).. In adults, there were no statistically significant differences between indiplon and placebo on the VAS-sleepiness, DSST, or SCT at any time-point for either dose. In contrast, a significant increase versus placebo in VAS-sleepiness was observed for both zopiclone (at 4 and 6 h post-dose; p < 0.0001 and p = 0.002, respectively) and zolpidem (at 4 h post-dose; p = 0.042). In the elderly, there were no statistically significant differences between indiplon 5 mg and placebo on the VAS-sleepiness, DSST, or SCT at any time-point. DSST was significantly reduced for indiplon 10 mg versus placebo at 4 h only (p = 0.022), compared with a significant reduction in DSST for zopiclone at both 4 and 8 h post-dose (p = 0.002 and p = 0.003, respectively). In adults, the overall incidence of adverse events was higher on zopiclone compared to indiplon, zolpidem, and placebo. In the elderly, the incidence of adverse events was similar for indiplon, zopiclone, and placebo. Potential limitations of the current study include recruitment of healthy volunteers and the use of a limited pharmacodynamic battery.. Indiplon, at doses of 10 mg in adults and 5 mg in the elderly, was not associated with next day residual sedation or impairment in simple cognitive and psychomotor tasks when administered during the night 4 h prior to awakening.

Topics: Adult; Aged; Aged, 80 and over; Azabicyclo Compounds; Benzodiazepines; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypnotics and Sedatives; Male; Middle Aged; Pain Measurement; Piperazines; Psychological Tests; Psychometrics; Pyridines; Reference Values; Sleep Initiation and Maintenance Disorders; Thiophenes; Time Factors; Zolpidem

Tiagabine is an anticonvulsant drug which may also have sleep-enhancing properties. It acts by inhibiting reuptake at the gamma-aminobutyric acid (GABA) transporter (GAT-1).. The aim of the study was to determine whether tiagabine acted as a discriminative stimulus and, if so, whether other GABAergic compounds would generalise to it.. Rats were trained to discriminate tiagabine (30 mg/kg p.o.) from vehicle, and generalisation to drugs that modulate GABA was assessed.. Gaboxadol (5-20 mg/kg p.o.), a selective extrasynaptic GABA A agonist, generalised to tiagabine, although the extent of the generalisation was inconclusive. Indiplon (1 mg/kg p.o.), a benzodiazepine-like hypnotic, also partially generalised to tiagabine, although zolpidem and S-zopiclone did not. Baclofen, a GABA B receptor agonist, and gabapentin, which increases synaptic GABA, did not generalise to tiagabine. (+)-Bicuculline (3 mg/kg i.p.), a GABA A receptor antagonist, blocked the tiagabine cue, but the less brain-penetrant salt form, bicuculline methochloride, had no effect.. These data suggest that tiagabine generates a discriminative stimulus in rats, and provides a central GABA-mediated cue, but is distinct from the other GABAergic compounds tested.

Topics: Administration, Oral; Amines; Animals; Anticonvulsants; Azabicyclo Compounds; Baclofen; Benzodiazepines; Bicuculline; Brain; Cyclohexanecarboxylic Acids; Discrimination Learning; Dose-Response Relationship, Drug; GABA Agents; GABA Agonists; GABA Antagonists; GABA Plasma Membrane Transport Proteins; Gabapentin; gamma-Aminobutyric Acid; Generalization, Stimulus; Hypnotics and Sedatives; Injections, Intraperitoneal; Isoxazoles; Male; Nipecotic Acids; Piperazines; Pyridines; Rats; Thiophenes; Tiagabine; Zolpidem

Topics: Acetamides; Age Factors; Azabicyclo Compounds; Benzodiazepines; Humans; Hypnotics and Sedatives; Piperazines; Pyridines; Pyrimidines; Sleep Wake Disorders; Thiophenes; Trazodone; Zolpidem