Disease relevance of Sonata

• In a separate experiment, observable behavioral effects (e.g., ataxia and procumbent posture) were quantified after administration of alprazolam, zaleplon, and QH-ii-066 [1].
• This improved risk profile includes: the effects of zaleplon on psychomotor and cognitive performance; tolerance, withdrawal and rebound; respiratory depression; sleep architecture; and other treatment-emergent adverse effects [2].
• MATERIALS AND METHODS: Twenty-five patients with thalassemia major had liver and myocardial T2* assessment using a Picker Edge 1.5T Scanner and a Siemens Sonata 1.5T scanner, with similar gradient echo sequences [3].
• Real-time TrueFISP visualization of swallowing was performed in 8 volunteers and 6 patients with dysphagia using a 1.5 T scanner (Magnetom Sonata, Siemens, Erlangen Germany) equipped with high-performance gradients (amplitude 40 mT/m) [4].
• METHODS: A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18) [5].

Psychiatry related information on Sonata

• Zaleplon does not appear to cause rebound insomnia, residual sedation, or adversely affect psychomotor function [6].
• Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance [7].
• There was no evidence of rebound insomnia or withdrawal symptoms after discontinuation of 4 weeks of zaleplon treatment [8].
• MEASUREMENTS AND RESULTS: Zaleplon allowed participants to obtain significantly more slow-wave sleep than under placebo [9].
• Zolpidem 20 mg (twice the therapeutic dose) produced more psychomotor impairment at the 1.25-hour assessment than did any of the other active treatments, including zaleplon 20 mg [7].

High impact information on Sonata

• METHOD: Ten healthy male volunteers received single oral doses of placebo, 10 mg zaleplon, 20 mg zaleplon, 10 mg zolpidem, and 20 mg zolpidem in a double-blind, 5-condition crossover study, with 48 hours elapsing between trials [10].
• Although zaleplon has a much lower bioavailability (30%), the treatment dose is similar to zolpidem and zopiclone (bioavilaibility of 70%) because of the increased potency of zaleplon [11].
• The pharmacokinetics and pharmacodynamics of zaleplon, zolpidem and zopiclone are significantly different from benzodiazepines [11].
• Residual effects of middle-of-the-night administration of zaleplon and zolpidem on driving ability, memory functions, and psychomotor performance [12].
• Compounds selective for alpha1 subunit-containing GABAA receptors (zolpidem, zaleplon, CL218,872) engendered relatively weak increases in the rates of suppressed responding [13].

Chemical compound and disease context of Sonata

• In a rat vigilance paradigm, indiplon, zolpidem, and zaleplon produced performance deficits over a dose range consistent with their sedative effects, although indiplon alone showed no significant increase in response latency [14].
• Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance [15].

Biological context of Sonata

• Changes in GABA(A) receptor gene expression induced by withdrawal of, but not by long-term exposure to, zaleplon or zolpidem [16].
• Pharmacokinetic analyses revealed CL 284,846 to be absorbed and eliminated rapidly (Tmax = 0.9-1.5 hr, T 1/2 = 0.9-1.1 hr), with a dose-proportional AUC (area under cure) [17].
• The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, zaleplon and zopiclone, e.g. in clinical and forensic toxicology [18].
• Clinically important drug interactions with zopiclone, zolpidem and zaleplon [19].
• The benzodiazepine binding site on the GABA(A) receptor is the target for the majority of hypnotics, including the nonbenzodiazepine 'Z drugs' (zaleplon, zolpidem, zopiclone and eszopiclone) [20].

Anatomical context of Sonata

• The results indicate that zaleplon taken by a nursing mother is transferred through breast milk to her infant in very small quantities that are unlikely to be clinically important [21].
• METHODS: At 1.5 T (Magnetom Sonata, Siemens), 30 symptomatic patients with 30 left internal thoracic artery grafts were examined 6 years after minimally invasive surgical intervention [22].
• In a binding study, zaleplon displaced bound [(3)H]flunitrazepam from membrane preparations from the rat hippocampus with an IC(50) of 4,454.5 nM [23].
• Zaleplon was 14.3 times more potent at inhibiting [3H]flunitrazepam binding to membrane preparations of the cerebellum than to membrane preparations of the spinal cord [24].
• Thin slices (2.5mm) were acquired of the cerebellar region containing the cerebellar nuclei with high spatial resolution (matrix size 128x128x10) using a Siemens 1.5T Sonata system [25].

Associations of Sonata with other chemical compounds

• These effects of zaleplon and zolpidem on GABA(A) receptor gene expression are consistent with the reduced tolerance liability of these drugs, compared with that of diazepam, as well as with their ability to induce both physical dependence and withdrawal syndrome [16].
• The 5-HT1A agonist buspirone (1.0-10.0 mg/kg) and the barbiturate pentobarbital (3.0-17.0 mg/kg) failed to substitute for CL 284,846 up to rate-decreasing doses [26].
• Effect of zaleplon on digoxin pharmacokinetics and pharmacodynamics [27].
• Inhibition of zaleplon metabolism by cimetidine in the human liver: in vitro studies with subcellular fractions and precision-cut liver slices [28].
• Healthy adult volunteers were given a dose of zaleplon 10 mg alone, a dose of ibuprofen 600 mg alone, or a dose of zaleplon 10 mg and a dose of ibuprofen 600 mg concomitantly in an open-label, randomized, three-period crossover study [29].

Gene context of Sonata

• Metabolism of Zaleplon by human hepatic microsomal cytochrome P450 isoforms [30].
• Aldehyde oxidase-dependent marked species difference in hepatic metabolism of the sedative-hypnotic, zaleplon, between monkeys and rats [31].
• Zaleplon-induced coma and bluish-green urine: possible antidotal effect by flumazenil [32].
• METHODS: Study 1: two mouse groups were exposed to music continuously for 10 hours per day for 10 weeks (Group I: Mozart's Sonata K.448, Group II: Beethoven's Fur Elise) [33].
• Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase [34].

Analytical, diagnostic and therapeutic context of Sonata

• Using a stethoscope, we relied on our skills in inspection, palpation, percussion, auscultation, as well as echocardiography and phonocardiography to diagnose a patient whose murmur was very reminiscent of the D-sharp pizzicato in the Cello Sonata in F, Opus 99, by Johannes Brahms [35].
• Zaleplon was well tolerated in clinical trials [36].
• This multicenter study compared the efficacy and safety of 3 doses of zaleplon with those of placebo in outpatients with DSM-III-R insomnia [8].
• In addition, the zaleplon-induced increase in the energy of the delta frequency band was antagonized by pretreatment with flumazenil (1 mg/kg, i.v.), which did not affect the spontaneous EEG alone [24].
• Oral administration of zaleplon and the reference drugs dose-dependently lessened the step-through latency in the test session of a passive avoidance task and increased the latency for reaching the hidden platform in the Morris water maze task, indicating the amnesic effect of the test drugs [23].

References