Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT(1) and MT(2) melatonin receptors. Ramelteon's half-life is longer than that of melatonin, being metabolized in the body to four main metabolites, M-I, M-II, M-III, and M-IV. M-II has an affinity to MT(1) and MT(2) of about one-tenth of the parent compound, but its concentration in the circulation exceeds that of ramelteon by more than an order of magnitude. Ramelteon is effective in decreasing latency to persistent sleep and increasing total sleep time in freely moving monkeys. A number of clinical studies have been undertaken to study the efficacy of ramelteon in subjects with chronic insomnia. In almost all of these studies, ramelteon, in various doses of 4, 8, or 16 mg most commonly, significantly reduced sleep latency and increased sleep duration. Its primary action in sleep promotion is not a generalized gamma-aminobutyric (GABA)-ergic central nervous system depression, but rather it acts as a melatonergic agonist in the suprachiasmatic nucleus (and at other central nervous system sites), from where downstream processes, including GABA-ergic effects, are controlled via the hypothalamic sleep switch. Unlike other commonly prescribed hypnotic drugs, ramelteon is not associated with next morning hangover effects or reductions in alertness, nor has it been shown to cause withdrawal symptoms. The adverse symptoms reported with ramelteon are mild. All long-term investigations that have been carried out support the conclusion that ramelteon is a well tolerated and effective drug for the treatment of insomnia.
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PMID:Ramelteon: a review of its therapeutic potential in sleep disorders. 1956 3

Current pharmacological treatment of insomnia involves the use of sedative-hypnotic benzodiazepine and non-benzodiazepine drugs. Although benzodiazepines improve sleep, their multiple adverse effects hamper their application. Adverse effects include impairment of memory and cognitive functions, next-day hangover and dependence. Non-benzodiazepines are effective for initiating sleep but are not as effective as benzodiazepines for improving sleep quality or efficiency. Furthermore, their prolonged use produces adverse effects similar to those observed with benzodiazepines. Inasmuch as insomnia may be associated with decreased nocturnal melatonin, administration of melatonin is a strategy that has been increasingly used for treating insomnia. Melatonin can be effective for improving sleep quality without the adverse effects associated with hypnotic-sedatives. Ramelteon, a synthetic analog of melatonin which has a longer half life and a stronger affinity for MT1 and MT2 melatonergic receptors, has been reportedly effective for initiating and improving sleep in both adult and elderly insomniacs without showing hangover, dependence, or cognitive impairment. Insomnia is also a major complaint among patients suffering from depressive disorders and is often aggravated by conventional antidepressants especially the specific serotonin reuptake inhibitors. The novel antidepressant agomelatine, a dual action agent with affinity for melatonin MT1 and MT2 receptors and 5-HT2c antagonistic properties, constitutes a new approach to the treatment of major depressive disorders. Agomelatine ameliorates the symptoms of depression and improves the quality and efficiency of sleep. Taken together, the evidence indicates that MT1/MT2 receptor agonists like ramelteon or agomelatine may be valuable pharmacological tools for insomnia and for depression-associated insomnia.
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PMID:Melatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics? 2145 40

Alcohol hangover is a temporary state described as the unpleasant next-day effects after binge-like drinking. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. Affective behavior is impaired during the acute phase of alcohol intoxication; however, no reports indicate if similar effects are observed during withdrawal. The aim of this work was to study the time-extension and possible fluctuations in affective behavior during a hangover episode. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8g/kg BW) (hangover group). Anxiety, fear-related behavior and despair phenotype were evaluated at a basal point (ZT0) and every 2h up to 20h after blood alcohol levels were close to zero (hangover onset). Also, anhedonia signs and pain perception disabilities were studied. Mice exhibited an increase in anxiety-like behavior during 4h and 14h after hangover onset when evaluated by the elevated-plus maze and open field test respectively (p<0.05). Fear-related behavior was detected in hangover animals by the increase of freezing and decrease of line crossings and rearing frequency during 16h after hangover onset (p<0.001). Depression signs were found in hangover mice during 14h (p<0.05). Hangover mice showed a significant decrease in pain perception when tested by tail immersion test at the beginning of hangover (p<0.05). Our findings demonstrate a time-extension between 14 and 16h for hangover affective impairments. This study shows the long lasting effects of hangover over the phase of ethanol intoxication.
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PMID:Alterations in affective behavior during the time course of alcohol hangover. 2385 Mar 52

The aim of the current study was to investigate what impact a state of alcohol hangover (AH) has upon everyday prospective memory (PM; memory for future events/intentions). Previous research has shown that the AH has a detrimental effect upon cognitive abilities, including memory and attentional deficits. No published research articles to date have focused upon what impact AH might have upon everyday memory, of which PM is a good example. The current study compared an AH group (AHG) with a non-hangover group (NHG) on PM. Since other drug use, anxiety and depression can affect PM independent of the AH, these covariates were controlled for in the study. Fifty-eight young adults studying at university participated in this between-subjects design study-25 in the AHG and 33 in the NHG. The Prospective Remembering Video Procedure (PRVP) measured PM. The Acute Hangover Rating Scale confirmed a state of AH and a Digital Breath Analyzer Test measured their BAC. The Hospital Anxiety and Depression Scale gauged levels of anxiety and depression and a Recreational Drug Use Questionnaire (RDUQ) measured alcohol and other drug use. Anyone who reported having used an illicit substance (e.g., cannabis, ecstasy) or who smoked, were excluded from the study. After controlling for age, alcohol units per week, years spent drinking alcohol, anxiety and depression scores, a one-way analysis of covariance (ANCOVA) revealed that the AHG (mean = 5.16) recalled significantly fewer items on the PRVP than the NHG (mean = 7.51)-F (1,52) = 5.69, p < 0.05. Overall, it appeared that a state of AH significantly impaired PM, which was not attributable to age, alcohol use, or anxiety or depression indices. Given the importance of PM to everyday activities, such as remembering to keep appointments or to take an important medication on time, this finding may have farther-reaching implications. These findings should also be used to educate young adults and health professionals dealing with the consequences with regards the dangers of alcohol misuse.
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PMID:A State of Alcohol Hangover Impedes Everyday Prospective Memory. 3028 10


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