Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All-night sleep was polygraphically monitored from ten normal volunteers who took placebo and three dosage levels of a new benzodiazepine hypnotic, SCH 16134, in a double-blind, crossover design. All dosages of the drug decreased the time to fall asleep, and the two highest dosages also decreased interspersed wakefulness. REM sleep was suppressed, but slow-wave sleep was not affected in this experiment. The subjective quality of sleep was improved by the new hypnotic. One subject reported that he felt lethargic the day after the largest dose.
 ...
PMID:The effect of a new benzodiazepine on the polygraphically monitored sleep of normal volunteers. 1 91

The sedative effect of SCH 34826, an enkephalinase inhibitor, was evaluated by studying electroencephalographic (EEG) activity, behaviour and the sleep-waking cycle in the rat. The reference opioid, morphine, was used for comparison. After administration of morphine (10 mg/kg s.c.) the rats were motionless and stuporous at first and then hyperactive. An increase of slow wave sleep, at the expense of both wakefulness and REM sleep was recorded, with high-amplitude slow wave bursts appearing in the EEG tracings during the waking, albeit stuporous, phase. Relative spectral power in the 1-4 and 12-16 Hz bands was increased and there was a shift of the dominant frequency to a lower frequency. The specific opioid antagonist, naltrexone, readily reversed most of these effects. The drug SCH 34826 (10-100 mg/kg p.o.) had no effect on the parameters examined; large doses (300 and 1000 mg/kg p.o.) induced restlessness in some animals, resulting in increased waking. This effect was antagonized by naltrexone. The data indicate that SCH 34826, at doses far greater than those proposed for clinical use, is devoid of sedative liability and does not induce any of the behavioural or EEG effects typical of morphine.
 ...
PMID:Effects of the enkephalinase inhibitor SCH 34826 on the sleep-waking cycle and EEG activity in the rat. 232 30

Hypnotic efficacy and safety of 3 weeks of daily doses of 2 mg lorazepam or 30 mg flurazepam were compared in a double-blind cross-over study in eight chronic insomniacs between the ages of 29 and 60 years. Subjects were monitored in the sleep laboratory twice weekly for a total of 25 nights. Also, subjective estimates of sleep, vigilance tests, and adverse effects were recorded throughout the study. Findings indicated lorazepam performed better than flurazepam in most sleep parameters. With lorazepam there was improvement from baseline in percentage of sleep time (P less than .05); in total wake time after sleep onset (P less than .01) and in last third of night (P less than .05); in percentage of stage 2 (P less than .05) (weeks 1, 2, 3) and in percentage of night in stage 4 (weeks 2 and 3). Only total wake time from baseline improved (P less than .05) with flurazepam (week 2). Objective and subjective sleep parameters did not correlate well for either drug. Neither drug impaired REM sleep or vigilance test performance. Side effects (grogginess, lethargy; flurazepam only) were few and none was unexpected; neither rebound insomnia nor early morning insomnia occurred with either drug. In summary, both lorazepam 2 mg at bedtime and flurazepam 30 mg at bedtime were found to be effective and safe for treating chronic insomnia, as measured by parameters of sleep and daytime functioning. Lorazepam had more favorable effects on sleep than did flurazepam.
 ...
PMID:Comparison of lorazepam and flurazepam as hypnotic agents in chronic insomniacs. 328 Jun 15

Wake-promoting agents such as modafinil are used in the clinic as adjuncts to antidepressant therapy in order to alleviate lethargy. The wake-promoting action of histamine H(3) receptor antagonists has been evidenced in numerous animal studies. They may therefore be a viable strategy for use as an antidepressant therapy in conjunction with selective serotonin reuptake inhibitors. JNJ-28583867 (2-Methyl-4-(4-methylsulfanyl-phenyl)-7-(3-morpholin-4-yl-propoxy)-1,2,3,4-tetrahydro-isoquinoline) is a selective and potent histamine H(3) receptor antagonist (K(i)=10.6 nM) and inhibitor of the serotonin transporter (SERT) (K(i)=3.7 nM), with 30-fold selectivity for SERT over the dopamine and norepinephrine transporters. After subcutaneous administration, JNJ-28583867 occupied both the histamine H(3) receptor and the SERT in rat brain at low doses (<1 mg/kg). JNJ-28583867 blocked imetit-induced drinking (3-10 mg/kg i.p.), confirming in vivo functional activity at the histamine H(3) receptor and also significantly increased cortical extracellular levels of serotonin at doses of 0.3 mg/kg (s.c.) and higher. Smaller increases in cortical extracellular levels of norepinephrine and dopamine were also observed. JNJ-28583867 (3-30 mg/kg p.o.) showed antidepressant-like activity in the mouse tail suspension test. JNJ-28583867 (1-3 mg/kg s.c.) caused a dose-dependent increase in the time spent awake mirrored by a decrease in NREM. Concomitantly, JNJ-28583867 produced a potent suppression of REM sleep from the dose of 1 mg/kg onwards. JNJ-28583867 has good oral bioavailability in the rat (32%), a half-life of 6.9 h and a C(max) of 260 ng/ml after 10 mg/kg p.o. In summary, JNJ-28583867 is a combined histamine H(3) receptor antagonist-SERT inhibitor with in vivo efficacy in biochemical and behavioral models of depression and wakefulness.
 ...
PMID:Pharmacological characterization of JNJ-28583867, a histamine H(3) receptor antagonist and serotonin reuptake inhibitor. 1776 21

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects 1 in 68 children in the United States. Even though it is a common disorder, only two medications (risperidone and aripiprazole) are approved by the U.S. Food and Drug Administration (FDA) to treat symptoms associated with ASD. However, these medications are approved to treat irritability, which is not a core symptom of ASD. A number of novel medications, which have not been approved by the FDA to treat ASD have been used off-label in some studies to treat ASD symptoms, including medications approved for Alzheimer's disease. Interestingly, some of these studies are high-quality, double-blind, placebo-controlled (DBPC) studies. This article systematically reviews studies published through April, 2014, which examined the use of Alzheimer's medications in ASD, including donepezil (seven studies, two were DBPC, five out of seven reported improvements), galantamine (four studies, two were DBPC, all reported improvements), rivastigmine (one study reporting improvements), tacrine (one study reporting improvements), and memantine (nine studies, one was DBPC, eight reported improvements). An evidence-based scale was used to rank each medication. Collectively, these studies reported improvements in expressive language and communication, receptive language, social interaction, irritability, hyperactivity, attention, eye contact, emotional lability, repetitive or self-stimulatory behaviors, motor planning, disruptive behaviors, obsessive-compulsive symptoms, lethargy, overall ASD behaviors, and increased REM sleep. Reported side effects are reviewed and include irritability, gastrointestinal problems, verbal or behavioral regression, headaches, irritability, rash, tremor, sedation, vomiting, and speech problems. Both galantamine and memantine had sufficient evidence ranking for improving both core and associated symptoms of ASD. Given the lack of medications approved to treat ASD, further studies on novel medications, including Alzheimer's disease medications, are needed.
...
PMID:The use of medications approved for Alzheimer's disease in autism spectrum disorder: a systematic review. 2520 86

We describe a 70-year-old man who, after a viral encephalitis associated with pneumonia, progressively developed a parkinsonism associated with lethargy. Encephalitis manifested with persistent hiccups, seizures and impairment of consciousness. After 2 weeks, the initial neurologic symptoms subsided and the patient progressively developed movement disorders (rigidity and bradykinesia, resistant to L-DOPA), lethargy and behavioral hypersomnia. Magnetic resonance imaging showed thalamic and hippocampal signal abnormalities, immunohistochemistry on a mouse brain substrate revealed serum autoantibodies binding to the brainstem neuropil. Polysomnographic monitoring was consistent with a very severe disruption of sleep: the sleep-wake cycle was fragmented, and the NREM-REM ultradian cycle was irregular. Intravenous immune globulin therapy resulted in the complete reversal of the movement and the sleep disorders. Our observation confirms that parkinsonism and sleep disorders may be consequences of encephalitis, that an immune-mediated pathogenesis is likely, and, consequently, that immunotherapy can be beneficial in these patients. The polysomnographic monitoring suggests that lethargia, rather than a mere hypersomnia, is the result of a combination between sleep disruption and altered motor control.
 ...
PMID:Post-Encephalitic Parkinsonism and Sleep Disorder Responsive to Immunological Treatment: A Case Report. 2711 63