Zolpidem chemical structure
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Ambien

Zolpidem is a prescription drug used for the short-term treatment of insomnia (sleeping pill). It works quickly (usually within 15 minutes) and has a short half-life (2-3 hours), but will last longer in patients with hepatic failure. Some trade names of zolpidem are Ambien®, Stilnox®, Stilnoct®, or Myslee®. more...

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Its sedative effects are similar to those of the benzodiazepines, but it is actually classified as an imidazopyridine, and the anticonvulsant and muscle relaxant effects only appear at 10 and 20 times the dose required for sedation, respectively. For that reason, it has never been approved for either muscle relaxation or seizure prevention. Such drastically increased doses are likely to induce one or more negative side effects, including hallucinations and/or amnesia.

The patent on zolpidem is held by the French pharmacutical corporation Sanofi-Aventis.

Uses

Zolpidem is approved for the short-term treatment of insomnia, but it has been studied for nightly use up to six months in a single-blind, open-label trial published in 1991, an open-label study lasting 180 days published in 1992 (with continued efficacy in patients who had kept taking it as of 180 days after the end of the trial), and in an open-label trial lasting 179 days published in 1993.

The United States Air Force uses zolpidem under trade name Ambien® as "no-go pills" to help the pilots sleep after the mission; another drug used for the same purpose is temazepam (Restoril®). (Cf. the "go-pills", amphetamine served under the name Dexedrine® as a stimulant for the pilots, or its recent modafinil (Provigil®) replacement).

It is also used off-label to treat restless leg syndrome.

As is the case with many prescription sedative/hypnotic drugs, zolpidem is sometimes used by stimulant users to "come down" after the use of stimulants such as methamphetamine, cocaine, methylenedioxymethamphetamine (MDMA), or pharmaceutical amphetamines.

Mechanism of action

In 1990, Pritchett and Seeburg noted that zolpidem binds with high affinity to the α1-, and with medium affinity to the α2- and α3-GABAA receptor subunits, and found that it had no affinity for the α5 subunit. Two years later, zolpidem was noted to have a high affinity for ω1-benzodiazepine receptors, a low affinity for ω2 and a very low affintity for ω3, respectively by Ruano et al in 1992. In other words, it has the highest affinity for ω1 binding sites on α-1GABAA receptor subunits, and it is this that mediates its sedative and weak anticonvulsant properties.

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Study links PCOS to depression
From OB/GYN News, 11/15/05 by Bruce K. Dixon

MONTREAL -- A total of 35% of those with polycystic ovary syndrome also had depression in a case-control study of 206 women.

"We recommend that women with PCOS should be routinely screened and adequately treated for depression," study investigator Elizabeth M. Hollinrake said at the joint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Among women with PCOS, the odds ratio was 5.11 for newly diagnosed depression and 4.23 for depression overall (newly diagnosed and previously diagnosed depression), compared with controls who did not have PCOS, said Ms. Hollinrake, who is a third-year medical student at the University of Iowa, Iowa City.

In an interview, the study's lead author, Anuja Dokras, M.D., Ph.D., noted that the results also show for the first time that depression in PCOS patients is significantly associated with both high body mass index (BMI) and insulin resistance.

"Between 50% and 70% of women who are treated for depression recover completely, so this is an important target population that we should be both screening and treating," added Dr. Dokras of the University of Iowa Hospitals and Clinics in Iowa City.

The study, which earned a first-place award among the General Program Prize Papers that were presented during the meeting, compared a total of 103 PCOS patients with 103 controls.

Women with PCOS diagnosed by the Rotterdam criteria were recruited from a reproductive endocrinology clinic; women without PCOS who attend the gynecology clinic for an annual exam were the controls.

The study investigators used the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire to diagnose major depressive disorder and other depressive syndromes. The Beck Depression Inventory was used to score the severity of depression.

Chi square and t-testing were used to compare differences between women with PCOS and controls, and PCOS women with and without depression.

In the PCOS group, 35% (36 women) were classified as depressed, compared with 10.7% (11 women) in the control group, representing a statistically significant difference. Of these 47 women with depression, 22 were already on antidepressants when they entered the clinic, the study showed.

When these 22 women were not considered, the rate of newly diagnosed depression was 21% in the PCOS group and 3% in the control group.

Women with PCOS had a significantly higher mean BMI than did controls (34.9 vs. 25.4), as did the subset of PCOS women who were depressed, compared with those who screened negative, according to the investigators.

"Although increased BMI among the depressed women is in keeping with the literature, ours is the first study to show this correlation in depressed women with PCOS," Dr. Dokras said.

Among the study participants with PCOS, 11% of those with depression also had diabetes, compared with none of the women without depression; the depressed women also had significantly higher glucose, insulin, and qualitative insulin-sensitivity check index scores.

"Importantly, women with PCOS have higher androgen levels, so one would have expected that if that was the basis, we would find some correlation with depression. On the contrary, these data showed no association with androgens ... only with BMI and insulin resistance," Dr. Dokras said during the interview.

BY BRUCE K. DIXON

Chicago Bureau

Kate Johnson of the Montreal Bureau contributed to this report.

COPYRIGHT 2005 International Medical News Group
COPYRIGHT 2005 Gale Group

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