Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium oxybate (gamma-hydroxybutyrate; GHB) has demonstrated efficacy for the treatment of narcolepsy. However, there are reports of withdrawal following chronic abuse of illicit GHB which involve escalating both doses and dosing frequency. The present trial afforded an opportunity to test the hypothesis that chronic daily therapeutic dosing of sodium oxybate in narcoleptics does not cause withdrawal following abrupt cessation. Fifty-five narcoleptic patients, taking sodium oxybate (dose range 3-9 gm/night) for 7-44 months (mean 21 months), were randomized into a 2-week double-blind period: 29 patients received placebo and 26 continued to receive sodium oxybate. During this 2-week trial period, the following symptoms were reported in patients receiving placebo (N): anxiety (2), dizziness (1), insomnia (1) and somnolence (1). While these symptoms may represent possible symptoms of mild GHB withdrawal, they are also highly consistent with the returning symptoms of narcolepsy. We conclude there is minimal evidence of withdrawal symptoms following abrupt cessation of chronic sodium oxybate dosing in the therapeutic range.
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PMID:The abrupt cessation of therapeutically administered sodium oxybate (GHB) does not cause withdrawal symptoms. 1508 50

Amylobarbitone sodium, butobarbitone, quinalbarbitone sodium, and a placebo were compared in a controlled, double-blind trial in psychiatric patients with insomnia. An apparatus recording movement in bed is described, with sleep assessments by night nurses and patients. All three barbiturates significantly reduced movement and gave significantly longer, less broken and sounder sleep, without increased incidence of "hang-over." There was no follow-on effect from night to night. With effective doses there was no significant difference between these barbiturates in onset and duration of hypnotic action, although usually accepted as either short or intermediate acting.
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PMID:The actions of amylobarbitone sodium, butobarbitone and quinalbarbitone sodium upon insomnia and nocturnal restlessness compared in psychiatric patients. 1371 80

Cyclobarbitone, hexobarbitone, quinalbarbitone sodium, pentobarbitone sodium, phenobarbitone sodium, nealbarbitone and a placebo have been compared in a controlled double-blind trial in twenty-four psychiatric patients with insomnia. Each of the barbiturates significantly prolonged sleep and hastened its onset. They also reduced the patients' motility, recorded by an electronic apparatus attached to the bed. There was no clear difference between these barbiturates in onset and duration of action during the 8 hr of recording; some effect upon sleep or motility was present throughout this period. Differences between compounds were of degree rather than of duration of action. Pentobarbitone, quinalbarbitone and phenobarbitone were most effective; cyclobarbitone and hexobarbitone were less effective; nealbarbitone had only a weak hypnotic action.
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PMID:A comparison of the effects of six barbiturates and a placebo on insomnia and motility in psychiatric patients. 1395 93

Jujuboside A (JuA) is a main component of jujubogenin extracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traditional medicine for the treatment of insomnia and anxiety. Previously, we reported the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, the present study was carried out to examine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocampus. Microdialysis coupled with high-performance liquid chromatography (HPLC) was used to monitor the changes of Glu levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA. The results showed that penicillin increased the hippocampal Glu concentration (p < 0.01) and a high dose of JuA (0.1 g/L) significantly blocked penicillin-induced Glu release (p < 0.05). Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM). It was found that Glu (0.5 mM) induced an intracellular [Ca2+]i increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca2+ increase. The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA. These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action.
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PMID:Inhibitory effect of jujuboside A on glutamate-mediated excitatory signal pathway in hippocampus. 1453 Oct 16

Sodium oxybate, also known as gamma-hydroxybutyric acid (GHB), was discovered in 1960 and has been described both as a therapeutic agent with high medical value and, more recently, a substance of abuse. The naturally occurring form of this drug is found in various body tissues but has been studied most extensively in the CNS where its possible function as a neurotransmitter continues to be studied. Sodium oxybate has been approved in different countries for such varied uses as general anaesthesia, the treatment of alcohol withdrawal and addiction, and, most recently, cataplexy associated with narcolepsy. During the 1980s, easy access to GHB-containing products led to various unapproved uses, including weight loss, bodybuilding and the treatment of sleeplessness, sometimes with serious long-term effects. The availability of these unapproved and unregulated forms of the drug led to GHB and its analogues being popularised as substances of abuse and subsequent notoriety as agents used in drug-facilitated sexual assault, or 'date rape', eventually leading to the prohibition of GHB sales in the US. Legal efforts to control the sale and distribution of GHB and its analogues nearly prevented the clinical development of sodium oxybate for narcolepsy in the US. However, following extensive discussions with a variety of interested parties, a satisfactory solution was devised, including legislative action and the development of the Xyrem Risk Management Program. Amendments to the US Controlled Substances Act made GHB a schedule I drug, but also contained provisions that allow US FDA-approved products to be placed under schedule III. This unique, bifurcated schedule for sodium oxybate/GHB allowed the clinical development of sodium oxybate to proceed and, in July 2002, it was approved by the FDA as an orphan drug for the treatment of cataplexy in patients with narcolepsy as Xyrem(sodium oxybate) oral solution. To promote the safe use of sodium oxybate, as well as alleviate concerns over possible diversion and abuse following product approval, a proprietary restricted drug distribution system was created, called the Xyrem Success Program. Components of the programme include a centralised distribution and dispensing system, a physician and patient registry, compulsory educational materials for patients and physicians, a specially trained pharmacy staff, a method for tracking prescription shipments, and an initial post-marketing surveillance programme. The system has created a unique opportunity to provide both physician and patient education and ongoing patient counselling, promoting greater drug safety and enhanced patient compliance.
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PMID:The Xyrem risk management program. 1506 84

It has been reported that star fruit can lead to a fatal outcome in uremic patients. The intoxication syndrome consists of hiccups, mental confusion, dizziness, and vomiting. On the other hand, folk medicine uses teas and infusions of carambola leaves to treat headache, vomiting, cough, insomnia, and diabetes. This motivated us to determine if Averrhoa carambola can act on the contractility and automaticity of the guinea pig heart. We measured the atrial isometric force in stimulated left atria and determined the chronotropic changes in spontaneously beating right atria. The carambola leaf extracts (1.5 mg/ml) abolished the contractile force in a concentration-dependent manner. Among the crude, methanolic, ethanolic, aqueous, and acetic extracts, the aqueous one was the most potent (EC50 = 520 +/- 94 microg/ml; flavonoids and tannins are the main constituents; Na+ and K+ contents in 1.0 mg/ml of aqueous extract were 0.12 +/- 0.016 and 1.19 +/- 0.15 mM, respectively). The aqueous extract abolished the positive Bowditch staircase phenomenon and reduced the inotropic response to CaCl2 (0.17-8.22 mM), events that are dependent on the cellular Ca2+ inward current. The adrenergic, muscarinic or opioid membrane receptors do not seem to participate in the mechanism of action of the cardioactive substance(s). In spontaneously beating atria, the aqueous extract promoted a negative chronotropic effect that was antagonized by 0.1 microM isoproterenol bitartrate. With this agonist, the EC50 of the aqueous extract increased from 133 +/- 58 to 650 +/- 100 microg/ml. These data regarding the effect of A. carambola on guinea pig atrial contractility and automaticity indicate an L-type Ca2+ channel blockade.
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PMID:Negative inotropic and chronotropic effects on the guinea pig atrium of extracts obtained from Averrhoa carambola L. leaves. 1600 83

Hypnotic drugs, including benzodiazepine receptor ligands, barbiturates, antihistamines, and melatonin receptor ligands, are useful in treating insomnia, but clinicians should consider the relative abuse liability of these drugs when prescribing them. Two types of problematic hypnotic self-administration are distinguished. First, recreational abuse occurs when medications are used purposefully for the subjective "high." This type of abuse usually occurs in polydrug abusers, who are most often young and male. Second, chronic quasi-therapeutic abuse is a problematic use of hypnotic drugs in which patients continue long-term use despite medical recommendations to the contrary. Relative abuse liability is defined as an interaction between the relative reinforcing effects (i.e., the capacity to maintain drug self-administration behavior, thereby increasing the likelihood of nonmedical problematic use) and the relative toxicity (i.e., adverse effects having the capacity to harm the individual and/or society). An algorithm is provided that differentiates relative likelihood of abuse and relative toxicity of 19 hypnotic compounds: pentobarbital, methaqualone, diazepam, flunitrazepam, lorazepam, GHB (gamma-hydroxybutyrate, also known as sodium oxybate), temazepam, zaleplon, eszopiclone, triazolam, zopiclone, flurazepam, zolpidem, oxazepam, estazolam, diphenhydramine, quazepam, tra-zodone, and ramelteon. Factors in the analysis include preclinical and clinical assessment of reinforcing effects, preclinical and clinical assessment of withdrawal, actual abuse, acute sedation/memory impairment, and overdose lethality. The analysis shows that both the likelihood of abuse and the toxicity vary from high to none across these compounds. The primary clinical implication of the range of differences in abuse liability is that concern about recreational abuse, inappropriate long-term use, or adverse effects should not deter physicians from prescribing hypnotics when clinically indicated.
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PMID:Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. 1633 40

gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. It is likely that supraphysiological concentrations of GHB from exogenous administration produce qualitatively different neuronal actions than those produced by endogenous GHB concentrations. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Endogenous and exogenous GHB is rapidly and completely converted into CO(2) and H(2)O through the tricarboxylic acid cycle (Krebs cycle). Sodium oxybate has been observed to modulate sleep in nonclinical study participants, and sleep and wakefulness in clinical populations, including groups with insomnia, fibromyalgia and narcolepsy. In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.
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PMID:gamma-Hydroxybutyrate/sodium oxybate: neurobiology, and impact on sleep and wakefulness. 1714 Feb 79

Semen Ziziphus jujube (SZJ), the seeds of Ziziphus jujuba Mill. var. spinosa, is a kind of traditional Chinese medicine used for its action on insomnia. In order to analyze the effective component, we investigated and compared the sedative and hypnotic effects of three kinds of compounds, flavonoids, saponins, and polysaccharides. Flavonoids, saponins, and polysaccharides were extracted from SZJ and orally administered to mice separately at 17 g kg(-1) per day for certain days before animal tests. Spontaneous motility and coordinated movement tests were used to observe the effects of the three kinds of compounds on the mouse behavior, and sodium barbital-induced sleeping time of mouse were tested to analyze the effects of the three kinds of compounds on the sleep of mouse. Results show that flavonoids and saponins caused a significant reduction of walking time and coordinated movement ability of mouse, significantly prolonged its sleeping time at 40 mg kg(-1), ip, subthreshold dose and increased the sleeping number of animals at 50 mg kg(-1), ip, superthreshold dose induced by coeliac injection of sodium barbital. Polysaccharides did not show any significance in all animal tests. Comparative analysis showed that saponins had a more effective sedative and hypnotic function than that of flavonoids, polysaccharides did not show a sedative and hypnotic effect.
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PMID:Comparison of the sedative and hypnotic effects of flavonoids, saponins, and polysaccharides extracted from Semen Ziziphus jujube. 1747 19

A variety of molecules with novel mechanisms of action are currently being evaluated for their potential as treatments for sleep disorders. The GABA-A receptor complex remains an important target for hypnotic drugs (eg gaboxadol, indiplon). However, drugs acting through histamine, calcium channels and serotonin receptors may also be of interest for the treatment of insomnia. In the case of the 5HT2A subtype of serotonin receptors, several molecules which improve sleep maintenance and modify sleep architecture by increasing slow wave sleep are currently being tested (eg eplivanserin). Two new drugs with efficacy in excessive sleepiness (modafinil, sodium oxybate) have improved the treatment of this condition. However, the mechanisms of action of these agents are poorly understood. The recent discovery of the hypocretin arousal system in the hypothalamus may aid the identification of additional new drugs. An agonist at receptors for the pineal hormone melatonin is available in some countries (ramelteon) but is currently used only for the treatment of insomnia associated with difficulties of sleep onset. Additional melatonin receptor agonists are being developed and may have potential for treating several conditions including circadian rhythm disorders and depression.
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PMID:New perspectives for the treatment of disorders of sleep and arousal. 1765 96


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