Diazepam chemical structure
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Valium

Diazepam, market under brand names of: Valium, Seduxen; and in Europe Apozepam, Diapam, is a 1,4-benzodiazepine derivative, which possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Diazepam is used to treat anxiety and tension, and is the most effective benzodiazepine for treating muscle spasms. It is also used as a sedative premedication for various medical procedures, and to treat alcohol and opiate withdrawal symptoms. Occasionally, diazepam is used by military and paramilitary snipers to relax muscles and slow breathing for increased firing accuracy. Diazepam is a Schedule IV drug under the Convention on Psychotropic Substances. more...

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Diazepam is one of the 'standard benzodiazepines' most often used in clinics and for outpatients. It is enrolled in the WHO List of 'Essential Drugs'.

When introduced in 1963, it was the best of the new alternatives to barbiturates, drugs that could be deadly with an overdose. Diazepam (like the other benzodiazepines) did not have this danger, nor immediately obvious side effects, and became in widespread use to treat chronic anxiety. Diazepam was America's top-selling drug from 1969 to 1982, with peak sales in 1978 of 2.3 billion pills ($US600 million in sales).

However, it is now recognised that the drug is not as harmless as was first assumed. In the autumn of 1973, a report aired on the television show 60 Minutes attesting to the drug's addictiveness. This can occur in as little as four weeks. Following controversial and often polemic discussion prescriptions declined by nearly half in the 1980's and 1990's. Surprisingly, psychiatrists and neurologists have recently discovered new therapeutic fields for this 'old' drug diazepam (e.g. adjunctive treatment of extrapyramidal disorders, some forms of anxiety in children, and adjunctive treatment of spastic paresis); a process still ongoing.

Mode of action

In animals, diazepam appears to act on parts of the limbic system, the thalamus and hypothalamus, and induces calming effects. It binds in to specific benzodiazepine receptors, which are part of the GABA-receptors. When diazepam binds to this receptor, it causes an increase in the inhibitory effects of GABA. It is redistributed into tissues and fat deposits, and there is an adaptation of benzodiazepine receptors. In humans, tolerance to the sedative effects may develop within weeks, but tolerance to the anxiolytic efficiacy usually does not develop. Lorazepam, clonazepam and alprazolam show stronger anxiolytic effects compared to diazepam, but the former 3 drugs carry a particular high risk of abuse, misuse and psychological dependence.

Pharmacokinetics

Diazepam can be administered orally, intravenously or intramuscularly, or as a suppository. When taken orally, diazepam is rapidly absorbed and shows a fast onset of action. Absorption is much slower and more erratic when diazepam is given as an intramuscular injection. Diazepam is highly lipid-soluble and therefore crosses the blood-brain barrier easily. Diazepam is metabolised in the liver and it has a biphasic half-life. The half-life (t1/2α) is 20-100 hours, and its main active metabolite, desmethyldiazepam, has a half-life of 2-5 days. Diazepam's other active metabolites include, among others, temazepam and oxazepam. Diazepam and its metabolites are excreted into the urine.

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Foods to help you snooze: you need more sleep and you need to eat better. Here's how to do both at once - Active Nutrition
From Men's Fitness, 9/1/03 by Linda Formichelli

Pick up your head, wipe the drool from your chin, and pay attention. We know you're tired; after all, according to a 2002 National Sleep Foundation poll, 68% of American adults don't get the recommended eight hours of sleep needed for good health, safety, and optimum performance.

If you're one of the nearly two-thirds of Americans who have trouble in the sack--sleeping, that is--you don't need to pop Valium like an Eisenhower-era housewife to log in more shut-eye. We spoke with experts to find out which foods, herbs and supplements can help you bag more z's, and which ones are pulling the wool blanket over your eyes.

FOODS THAT SOOTHE

TURKEY

Picture Grandpa last Thanksgiving: asleep on the couch, head back, belt unbuckled--and it was only 6 p.m. It's not his eight decades, it's the turkey. Turkey contains tryptophan, an amino acid that converts to the slumber-promoting neurotransmitter serotonin. To feel the turkey lullaby, try eating a turkey sandwich an hour before bedtime.

WARM MILK

Like turkey, milk contains tryptophan, and the calcium and magnesium in milk help enhance the conversion of tryptophan to serotonin. As for whether there's any truth to the old tale about warm milk's sleep-inducing powers, the jury is still out.

"I have heard for years that warming the milk makes the tryptophan more bioavailable to the body," says David Edelberg, M.D., medical director of WholeHealth, a health center that provides integrative medicine, and author of The Healing Power of Vitamins, Minerals, and Herbs. "But no one has ever done a clinical study on warm milk vs. cold milk." If the thought of warm milk makes you feel all warm and fuzzy inside, go for it. If it makes you want to gag, quaff it cold. Either way, try a glass an hour before bedtime.

VALERIAN

Preliminary studies show that the herb valerian may improve sleep, but its effects are mild. "We still don't know the exact dose and what preparation is best," says Allison Sarubin-Fragakis, M.S., R.D., author of The Health Professional's Guide to Popular Dietary Supplements. "Also, one study showed that valerian--in a 900-milligram dose--created a hangover-like effect the next morning, so that's something to pay attention to."

Valerian is available in capsules, tablets, teas and tinctures. Sarubin-Fragakis recommends taking a dose that's less than 900 mg one hour before bed on an as-needed basis. Don't take valerian with any other sleep-promoting medications.

COMFORT FOODS

Chowing down on the foods your mama used to make--like mashed potatoes or mac and cheese--can make you feel as warm and soft as those goodies, which may help you catch a few more winks. "There are a lot of psychological interactions with food that we don't understand well," says Jeff Hampl, Ph.D., R.D., professor of nutrition at Arizona State University and a spokesperson for the American Dietetic Association. "But it's not surprising that if someone eats a comfort food, he'll start to feel pleasantly relaxed."

If you're feeling too stressed to sleep, try eating a snack that harkens back to the days when your biggest worry was whether to use the red Crayola or the green. But if your childhood comfort food was s'mores covered in caramel sauce, you should try a more adult alternative, such as oatmeal with cinnamon or low-fat chocolate pudding.

CARBOHYDRATES

Here's a good reason to nosh on carbohydrates: "Carbs cause blood sugar levels to rise, and that prompts the pancreas to put out more insulin," explains Ray Sahelian, M.D., author of Mind Boosters: A Guide to Natural Supplements That Enhance Your Mind, Memory, and Mood. "Insulin in the bloodstream facilitates the entry of tryptophan into the brain." And--say it it with us--tryptophan is converted into sleep-boosting serotonin. Sahelian suggests having vegetable soup, fruit salad, or a slice of low-fat cheese melted over whole-wheat bread with a slice of tomato one or two hours before bedtime.

MORE HYPE THAN HELP

MELATONIN

Available in pill form at health-food stores, melatonin plays a role in regulating your sleep-wake cycle. "As far as sleep assistance goes, the results in research are very mixed," says Sarubin-Fragakis. "There are so many factors to consider. How much should you take? Are you traveling east? Do you have delayed-sleep syndrome?" These variables have made it hard for any researchers to endorse melatonin as a sleep aid.

Sarubin-Fragakis advises against taking hormones while not under the care of a doctor. Instead, she recommends doing things that will maximize melatonin's production in the body: forgoing caffeine and alcohol, increasing exposure to light during the day, and not taking naps any longer than 30 minutes.

KAVA

Kava is used as a social drink in the South Pacific, much like light beer is in the U.S. Unlike a nice, icy brew, "kava tastes like dirt," says Sarubin-Fragakis. But despite its nasty flavor, kava does reduce anxiety, which can help you sleep.

However, the Food and Drug Administration is informing consumers about the risk of potential liver injury from the use of dietary supplements containing kava. Recent reports from health authorities in Germany, Switzerland, France, Canada and the United Kingdom have linked kava to at least 25 cases of liver toxicity, including hepatitis, cirrhosis and liver failure. Whether the ailments were caused by the kava itself or by impurities in the supplements is unknown.

Why you need your z's.

The relationship between sleep and your gray matter becomes clearer when you learn that the first step to any brainwashing (think cult) or serious interrogation (think CIA and Al Qaida) is to deprive the victim of sleep. Besides causing confusion, auditory hallucinations, and permanent morning breath, the withholding of such a basic and powerful rejuvenator is a form of torture itself. In fact, one study showed that given the choice between sex and uninterrupted slumber, sleep-deprived men chose to bag some z's.

Check out what we've learned about the effect sleep, or lack of it, has on your health, fitness, sex life and overall well-being.

* Just one night of sleep deprivation causes an increase in the release of the muscle-wasting hormone cortisol, says a study performed at the National University of Singapore. Cortisol also leads to fat deposition, what MEN'S FITNESS terms the "gut-butt syndrome."

* According to research published in the Archives of Internal Medicine, too little sleep is associated with an increased risk of cardiovascular disease.

* More than 100,000 automobile crashes (including 1,550 deaths) are attributed every year to drowsy driving, reports the National Highway Traffic Safety Administration.

* A profound, but reversible, decrease in sexual function has been found in men with serious sleep disturbances, due mostly to lowered testosterone levels, according to a study performed at the University of British Columbia in Vancouver.

* Research published in the American Journal of Human Biology shows that poor sleep quality contributes to obesity in teenagers.

Get the message? Now go to sleep.

--Mike Carlson

TOSSING, TURNING AND CHURNING

Just as some foods will help you zonk out, others will make you flip like a flapjack all night.

* A glass of wine may help you relax while you are awake, but alcohol can actually disrupt sleep. Alcohol also has a diuretic effect, which will send you scurrying to the john in the middle of the night.

* Caffeine is an obvious no-no, but remember that coffee isn't the only culprit; chocolate, tea and some sodas also pack a caffeinated punch.

* Resist your cravings for spicy food as bedtime nears. "If you eat something spicy and then lie down, you're more likely to have heartburn," says Jeff Hampl, Ph.D., R.D., professor of nutrition at Arizona State University.

* The same goes for greasy foods, which can be difficult to digest and can cause upset stomach and heartburn.

* Tyramine is an amino acid that causes the release of norepinephrine, a brain stimulant that can keep you awake, according to David Edelberg, M.D., author of The Healing Power of Vitamins, Minerals, and Herbs. Foods that contain tyramine include bacon, aged cheese, chocolate, ham, sausages and wine. Fortunately, lean proteins don't contain enough tyramine to impair your sleep.

COPYRIGHT 2003 Weider Publications
COPYRIGHT 2003 Gale Group

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