Ethanol, sedative effects

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

They found that a strain of mice that lacks the gene for NPY—NPY knockout mice—consume more ethanol than control mice and are less sensitive to ethanol s sedative effects. As would be expected if increased concentrations of NPY in the brain make mice more sensitive to ethanol, a strain of mice that overexpresses NPY drinks less alcohol than the controls even though their total consumption of food and liquid is normal. Work with other transgenic knockout mice support the central role in ethanol responses of signaling molecules that have long been believed to be involved (eg, GABA A, glutamate, dopamine, opioid, and serotonin receptors) and has helped build the case for newer candidates such as NPY and cannabinoid receptors, ion channels, and protein kinase C. 

Walsh JK, Humm T, Muehlbach MJ, Sugerman JL, Schweitzer PK. Sedative effects of ethanol at night. J Stud Alcohol 1991 52 597-600. 

The combination of phenobarbital and alcohol is dangerous, apart from their additive sedative effects. Barbi-tuates are detoxified by oxidation. Ethanol inhibits the reaction by being a competing sulKtiate for oxidation, allowing the baibituate level to remain high. 

Warnings/precautions Additive sedative effects with other CNS depressants (ethanol) tolerance and dependence may develop with prolonged use Serotonin syndrome may occur with other serotonergic drugs (i.e. MAO inhibitors) SSRIs may inhibit CYP450 liver enzymes ... 

Several studies describe the hypnotie activity of flavonoids. Apigenin is a flavonoid that showed sedative and antidepressant activity [367]. The flavonoids and indole alkaloids of P. incarnata L., also showed sedative effects [368]. Linarin, a flavonoid-isolated from Valeriana officinalis L. showed sedative and sleep-enhancing properties (Fernandez et al., 2004). The nonvolatile fraction of L. alba, extracted in ethanol, presented sedative and myorelaxing effects among the extracts tested, these possess the highest flavonoid content [296]. 

For a hydroalcoholic extract of Hypericum perforatum, produced by successive extraction of dried aerial parts with petroleum ether, 1,2-dichlorethane and ethanol (50 % v/v), a sedative effect in mice has been reported [123]. The authors observed a bell-shaped dose-response effect on spontaneous motility with maximal activity at an oral dose of 26.5 mg/kg p.o, while pentobarbital-induced sleeping time was most significantly prolonged at the lowest dose applied (13.25 mg/kg p.o.). No effect on neuromuscular transmission was observed in three different test models (chimney test, traction test and rota-rod test). After separation of the crude extract in fractions containing mainly flavones, naphthodianthrones or amino acids, it was not possible to clearly attribute the effect of the native extract to a particular group of constituents. Thus, the authors conclude that activity of the hydroalcoholic extract may results form the cumulative effects of different compound, but they do not offer any explanation for the lower activity of the extract at higher doses. 

Alcohol extract from saffron has been also examined for learning and memory, in step through (ST) and step down (SD) tests, in normal and in leaming-and memory-impaired mice. The results showed that this extract ameliorates the impairment effects of ethanol on learning and memory processes and possesses a sedative effect [85-87]. In addition, recent experiments have shown that crocin and crocetin derivatives inhibit promotion of tumor in mice [88]. 

Alcohol (ethanol) and sedative drugs Paroxetine does not appear to potentiate the sedative effects of psychomotor retardation induced by amyiobarbitai, aicohol, or oxazepam. 

A. Additive sedative effect with opioids, ethanol, and other sedatives. 

GHB has sedative, anxiolytic, and euphoric effects similar to ethanol, likely because of potentiation of cerebral GABAergic and dopaminergic activities. 

The withdrawal syndrome from ethanol includes anxiety, insomnia, possibly convulsions and visual hallucinations (delirium tremens - the Dts). It is treated or better still prevented by a calm environment, adequate (but not excessive) hydration, and careful monitoring, with the added use of anticon-vulsive/sedative agents, mainly benzodiazepines to prevent or treat convulsions. The preventive effects of benzodiazepines on withdrawal morbidity has been clearly demonstrated. There do not seem to be major differences between benzodiazepines, such as chlordiazepoxide or diazepam or others. Because of the abuse potential in these highly susceptible patients, these should be rapidly weaned, and proper prevention of relapse instituted. Other drugs such as meprobamate and clomethiazole (Hemineurin) are commonly used in some countries. The effectiveness... 

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