Zolpidem
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Zolpidem
Systematic (IUPAC) name
N,N-dimethyl-2-(6-methyl-2-p-tolylimidazo[1,2a]pyridin-3-yl)acetamide
Clinical data
Trade names
Ambien
AHFS/Drugs.c
monograph
om
MedlinePlus
a693025
Pregnancy cat. B3 (AU) C (US)
Legal status
Prescription Only (S4) (AU)
Schedule IV (US) CD (UK)[1]
Routes
Oral (tablet), Sublingual,
Oromucosal (spray)
Pharmacokinetic data
Bioavailability
70% (oral) 92% bound in
plasma
Metabolism
Hepatic – CYP3A4
Half-life
2 to 3 hours
Excretion
56% renal
34% fecal
Identifiers
CAS number
82626-48-0
ATC code
N05CF02
PubChem
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Formula
Mol. mass
SMILES
CID 5732
DB00425
5530
7K383OQI23
D08690
CHEBI:10125
CHEMBL911
Chemical data
C19H21N3O
307.395 g/mol
[show]
InChI
[show]
(what is this?) (verify)
Zolpidem (brand names Ambien, Ambien CR, Intermezzo, Stilnox,
Sublinox and Zolsana) is a prescription medication used for the treatment
of insomnia and some brain disorders. It is a short-acting
nonbenzodiazepine hypnotic of the imidazopyridine class [2] that
potentiates GABA, an inhibitory neurotransmitter, by binding to GABAA
receptors at the same location as benzodiazepines.[3] It works quickly,
usually within 15 minutes, and has a short half-life of two to three hours.
Zolpidem has not adequately demonstrated effectiveness in maintaining
sleep, unless delivered in a controlled-release (CR) form. However, it is
effective in initiating sleep.[4] Its hypnotic effects are similar to those of the
benzodiazepine class of drugs, but it is molecularly distinct from the
classical benzodiazepine molecule and is classified as an imidazopyridine.
Flumazenil, a benzodiazepine receptor antagonist, which is used for
benzodiazepine overdose, can also reverse zolpidem's sedative/hypnotic
and memory-impairing effects.[5][6]
As a muscle relaxant and anticonvulsant, the drug's effects are not evident
until dosages 10 and 20 times those required for sedation, respectively,
are reached.[7] For that reason, zolpidem has never been approved for
either muscle relaxation or seizure prevention. Such drastically increased
doses are also more inclined to induce one or more of the drug's adverse
side effects, including hallucinations and amnesia.
The United States patent for zolpidem was held by the French
pharmaceutical corporation Sanofi-Aventis.[8] On April 23, 2007, the U.S.
Food and Drug Administration (FDA) approved 13 generic versions of
zolpidem tartrate.[9] Zolpidem is available from several generic
manufacturers in the UK, as a generic from Sandoz in South Africa and
TEVA in Israel, as well as from other manufacturers such as Ratiopharm
(Germany).
On 2012, a study published in the BMJ Open journal revealed that
sleeping pills, including zolpidem, are associated with a higher risk of
death and cancer diagnosis. Nevertheless, the study showed only a link,
and did not prove the deaths were caused by the pills or by other
symptoms related to insomnia.[10]
On January 10, 2013, the Food and Drug Administration announced it is
requiring the manufacturer of Ambien and Zolpimist to cut the
recommended dosage for women in half, after laboratory studies showed
that the medicines can leave patients drowsy in the morning and at risk for
car accidents. The FDA recommended that manufacturers extend the new
dosage cuts to men as well, who process the drug at a faster rate;
however, the reasons men and women catabolize the drugs at different
rates are still unknown.[11] In May 2013, the FDA approved label changes
specifying new dosage recommendations for zolpidem products because
of concerns regarding next-morning impairment.[12]
Contents [hide]
1 Medical uses
2 Adverse effects
2.1 Tolerance, dependence, and withdrawal
2.2 Overdose
2.3 Detection in body fluids
3 Special precautions
3.1 Driving
3.2 Elderly
3.3 Gastroesophageal reflux disease
3.4 Pregnancy
4 Mechanism of action
4.1 Drug-drug interactions
5 Misuse
5.1 Recreational use
5.2 Date-rape drug
6 Usage
7 Research
8 References
9 Further reading
10 External links
Medical uses[edit]
Zolpidem tartrate 10 mg tablets
Clinicians prescribe zolpidem for short-term (usually about two to six
weeks) treatment of insomnia.[13] Zolpidem has not proven effective in
maintaining sleep, but addresses sleep-initiation problems.[4] The effect
over placebo is of marginal clinical benefit.[14]
Adverse effects[edit]
Various zolpidem pills
Side effects may include:
•
•
•
•
•
•
Headaches
Nausea
Vomiting
Dizziness
Anterograde amnesia
Hallucinations, through all physical senses, of varying intensity
• Delusions[citation needed]
• Altered thought patterns
• Ataxia or poor motor coordination, difficulty maintaining balance[15]
• Euphoria and/or dysphoria
• Increased appetite
• Increased or decreased libido
• Impaired judgment and reasoning
• Uninhibited extroversion in social or interpersonal settings
• Increased impulsivity
• When stopped, rebound insomnia may occur
Some users have reported unexplained sleepwalking[16][original research?]
while using zolpidem, as well as sleep driving, binge eating while asleep,
and performing other daily tasks while sleeping. Research by Australia's
National Prescribing Service found these events occur mostly after the first
dose taken, or within a few days of starting therapy.[17] Rare reports of
sexual parasomnia episodes related to zolpidem intake have also been
reported.[18] Sleepwalkers can sometimes perform these tasks as normally
as they might if they were awake. They can sometimes carry on complex
conversations and respond appropriately to questions or statements, so
much so that observers may believe them to be awake. This is in contrast
to "typical" sleep talking, which can usually be identified easily and is
characterised by incoherent speech that often has no relevance to the
situation or that is so disorganised as to be completely unintelligible.
Those under the influence of this medication may seem fully aware of their
environments, though they are still asleep. This can bring about concerns
for the safety of the sleepwalkers and others. These side effects may be
related to the mechanism that also causes zolpidem to produce its
hypnotic properties.[19] It is unclear whether the drug is responsible for the
behavior, but a class-action lawsuit was filed against Sanofi-Aventis in
March 2006 on behalf of those who reported symptoms.[20] Conversely, it
is possible some users believed they were asleep during these events
because they do not remember the events, due to the short-term memory
loss and anterograde amnesia side effects.
Residual 'hangover' effects, such as sleepiness and impaired psychomotor
and cognitive function, may persist into the day following nighttime
administration. Such effects may impair the ability of users to drive safely
and increase risks of falls and hip fractures.[21]
The Sydney Morning Herald in Australia in 2007 reported a man who fell
30 meters to his death from a high-rise unit balcony may have been
sleepwalking under the influence of Stilnox. The coverage prompted over
40 readers to contact the newspaper with their own accounts of Stilnox-
related automatism, and as of March 2007, the drug was under review by
the Adverse Drug Reactions Advisory Committee.[22][needs update]
In February 2008, the Australian Therapeutic Goods Administration
attached a boxed warning to zolpidem, stating, that "Zolpidem may be
associated with potentially dangerous complex sleep-related behaviors
that may include sleep walking, sleep driving, and other bizarre
behaviours. Zolpidem is not to be taken with alcohol. Caution is needed
with other CNS depressant drugs. Limit use to four weeks maximum under
close medical supervision."[23] This report received widespread media
coverage[24] after the death of Australian student Mairead Costigan, who
fell 20 m from the Sydney Harbour Bridge while under the influence of
Stilnox.[25]
Tolerance, dependence, and withdrawal[edit]
Ambien tablets
A review medical publication found long-term use of zolpidem is
associated with drug tolerance, drug dependence, rebound insomnia and
CNS-related adverse effects. It was recommended that zolpidem be used
for short periods of time using the lowest effective dose. Zolpidem 10 mg is
effective in treating insomnia when used intermittently no fewer than three
and no more than five pills per week for a period of 12 weeks.[26] The 15mg zolpidem dosage provided no clinical advantage over the 10-mg
zolpidem dosage.[27]
Nonpharmacological treatment options (e.g. cognitive behavioral therapy
for insomnia), however, were found to have sustained improvements in
sleep quality.[28] Animal studies of the tolerance-inducing properties have
shown that in rodents, zolpidem has less tolerance-producing potential
than benzodiazepines, but in primates the tolerance-producing potential of
zolpidem was the same as that of benzodiazepines.[29] Tolerance to the
effects of zolpidem can develop in some people in just a few weeks.
Abrupt withdrawal may cause delirium, seizures, or other severe effects,
especially if used for prolonged periods and at high dosages.[30][31][32]
When drug tolerance and physical dependence to zolpidem has
developed, treatment usually entails a gradual dose reduction over a
period of months to minimise withdrawal symptoms, which can resemble
those seen during benzodiazepine withdrawal. Failing that, an alternative
method may be necessary for some patients, such as a switch to a
benzodiazepine equivalent dose of a longer-acting benzodiazepine drug,
such as diazepam or chlordiazepoxide, followed by a gradual reduction in
dosage of the long-acting benzodiazepine. Sometimes for difficult-to-treat
patients, an inpatient flumazenil rapid detoxification program can be used
to detoxify from a zolpidem drug dependence or addiction.[33]
Alcohol has cross tolerance with GABAA receptor positive modulators such
as the benzodiazepines and the nonbenzodiazepine drugs. For this
reason, alcoholics or recovering alcoholics may be at increased risk of
physical dependency on zolpidem. Also, alcoholics and drug abusers may
be at increased risk of abusing and or becoming psychologically
dependent on zolpidem. It should be avoided in those with a history of
alcoholism, drug misuse, physical dependency, or psychological
dependency on sedative-hypnotic drugs. Zolpidem has rarely been
associated with drug-seeking behavior[citation needed], the risk of which is
amplified in patients with a history of drug or alcohol abuse.
Overdose[edit]
An overdose of zolpidem may cause excessive sedation, pin-point pupils,
or depressed respiratory function, which may progress to coma, and
possibly death. Combined with alcohol, opiates, or other CNS depressants,
it may be even more likely to lead to fatal overdoses. Zolpidem overdosage
can be treated with the benzodiazepine receptor antagonist flumazenil,
which displaces zolpidem from its binding site on the benzodiazepine
receptor to rapidly reverse the effects of the zolpidem.[34]
Detection in body fluids[edit]
Zolpidem may be quantitated in blood or plasma to confirm a diagnosis of
poisoning in hospitalized patients, provide evidence in an impaired driving
arrest, or to assist in a medicolegal death investigation. Blood or plasma
zolpidem concentrations are usually in a range of 30–300 μg/l in persons
receiving the drug therapeutically, 100–700 μg/l in those arrested for
impaired driving, and 1000–7000 μg/l in victims of acute overdosage.
Analytical techniques, in general, involve gas or liquid
chromatography.[35][36][37]
Special precautions[edit]
Driving[edit]
Use of zolpidem may impair driving skills with a resultant increased risk of
road traffic accidents. This adverse effect is not unique to zolpidem but
also occurs with other hypnotic drugs. Caution should be exercised by
motor vehicle drivers.[38] Studies showed that eight hours after a 10 mg
bedtime dose, 15% of women and 3% of men would have blood levels
which producing impaired driving skills; for a 12.5 mg extended-release
dose, the risk increased to 33% and 25%, respectively. Consequently, the
FDA recommended the dose for women be reduced and that prescribers
should consider lower doses for men.[39][40]
Elderly[edit]
The elderly are more sensitive to the effects of hypnotics including
zolpidem. Zolpidem causes an increased risk of falls and may induce
adverse cognitive effects.[41]
An extensive review of the medical literature regarding the management of
insomnia and the elderly found there is considerable evidence of the
effectiveness and durability of nondrug treatments for insomnia in adults of
all ages, and these interventions are underused. Compared with the
benzodiazepines, the nonbenzodiazepine (including zolpidem) sedativehypnotics appeared to offer few, if any, significant clinical advantages in
efficacy or tolerability in elderly persons. Newer agents with novel
mechanisms of action and improved safety profiles, such as the melatonin
agonists, were found to hold promise for the management of chronic
insomnia in elderly people. Long-term use of sedative-hypnotics for
insomnia lacks an evidence base and has traditionally been discouraged
for reasons that include concerns about such potential adverse drug
effects as cognitive impairment (anterograde amnesia), daytime sedation,
motor incoordination, and increased risk of motor vehicle accidents and
falls. In addition, the effectiveness and safety of long-term use of these
agents remain to be determined. More research is needed to evaluate the
long-term effects of treatment and the most appropriate management
strategy for elderly persons with chronic insomnia.[42]
Gastroesophageal reflux disease[edit]
Patients suffering from gastroesophageal reflux disease had reflux events
measured to be significantly longer when taking zolpidem than on placebo.
(The same trend was found for reflux events in patients without GERD).
This is assumed to be due to suppression of arousal during the reflux
event, which would normally result in a swallowing reflex to clear gastric
acid from the esophagus. Patients with GERD who take zolpidem thus
experience significantly higher esophageal exposure to gastric acid, which
increases the likelihood of developing esophageal cancer.[43]
Pregnancy[edit]
Zolpidem has been assigned to pregnancy category C by the FDA. Animal
studies have revealed evidence of incomplete ossification and increased
postimplantation fetal loss at doses greater than seven times the maximum
recommended human dose or higher; however, teratogenicity was not
observed at any dose level. There are no controlled data in human
pregnancy. In one case report, zolpidem was found in cord blood at
delivery. Zolpidem is only recommended for use during pregnancy when
benefits outweigh risks. [44]
Mechanism of action[edit]
Zaleplon and Zolpidem both are agonists at the GABA A ɣ 1 subunit. Due
to its selective binding, Zolpidem has very weak anxiolytic, myorelaxant,
and anticonvulsant properties but very strong hypnotic properties.[45]
Zolpidem binds with high affinity and acts as a full agonist at the α1containing GABAA receptors, about 10-fold lower affinity for those
containing the α2- and α3- GABAA receptor subunits, and with no
appreciable affinity for α5 subunit-containing receptors.[46][47] ω1 type
GABAA receptors are the α1-containing GABAA receptors and ω2 GABAA
receptors are the α2-, α3-, α4-, α5-, and α6-containing GABAA receptors. ω1
GABAA receptors are found primarily in the brain, whereas ω2 receptors
are found primarily in the spine. Thus, zolpidem has a preferential binding
for the GABAA-benzodiazepine receptor complex in the brain but a low
affinity for the GABAA-benzodiazepine receptor complex in the spine.[48]
Like the vast majority of benzodiazepine-like molecules, zolpidem has no
affinity for α4 and α6 subunit-containing receptors.[49] Zolpidem positively
modulates GABAA receptors, it is presumed by increasing the GABAA
receptor complex's apparent affinity for GABA without affecting
desensitization or peak current.[50] Like zaleplon (Sonata), zolpidem may
increase slow wave sleep but cause no effect on stage 2 sleep.[51]
A meta-analysis of the randomised, controlled, clinical trials that compared
benzodiazepines against nonbenzodiazepines such as zolpidem has
shown few consistent differences between zolpidem and benzodiazepines
in terms of sleep onset latency, total sleep duration, number of
awakenings, quality of sleep, adverse events, tolerance, rebound
insomnia, and daytime alertness.[52]
Drug-drug interactions[edit]
Notable drug-drug interactions with the pharmacokinetics of zolpidem
include chlorpromazine, fluconazole, imipramine, itraconazole,
ketoconazole, rifampicin, and ritonavir. Interactions with carbamazepine
and phenytoin can be expected based on their metabolic pathways, but
have not yet been studied. There does not appear to be any interaction
between zolpidem and cimetidine or ranitidine.[53][54] However, it was
noted in the same study that cimetidine did appear to prolong the hypnotic
effects of Zolpidem beyond its typical 3 hour duration, which is indicative of
some sort of metabolic interaction.[55]
Misuse[edit]
Recreational use[edit]
Zolpidem has a potential for either medical misuse when the drug is
continued long term without or against medical advice, or recreational use
when the drug is taken to achieve a "high".[56] The transition from medical
use of zolpidem to high-dose addiction or drug dependence can occur
when used without a doctor's recommendation to continue using it, when
physiological drug tolerance leads to higher doses than the usual 5 mg or
10 mg, when consumed through inhalation or injection, or when taken for
purposes other than as a sleep aid. Misuse is more prevalent in those who
have been dependent on other drugs in the past, but tolerance and drug
dependence can still sometimes occur in those without a history of drug
dependence. Chronic users of high doses are more likely to develop
physical dependence on the drug, which may cause severe withdrawal
symptoms, including seizures, if abrupt withdrawal from zolpidem
occurs.[57]
One case history reported a woman detoxifying from a high dose of
zolpidem experiencing a generalized seizure, with clinical withdrawal and
dependence effects reported to be similar to the benzodiazepine
withdrawal syndrome.[58]
Nonmedical use of zolpidem is increasingly common in U.S.A, Canada,
and the UK. Recreational users report that resisting the drug's hypnotic
effects can in some cases elicit vivid visuals and a body high.[59] Some
users have reported decreased anxiety, mild euphoria, perceptual
changes, visual distortions, and hallucinations.[60]
Other drugs, including the benzodiazepines and zopiclone, are also found
in high numbers of suspected drugged drivers. Many drivers have blood
levels far exceeding the therapeutic dose range suggesting a high degree
of excessive-use potential for benzodiazepines, zolpidem and
zopiclone.[61] U.S. Congressman Patrick J. Kennedy says that he was
using Zolpidem (Ambien) and Phenergan when caught driving erratically at
3AM.[62] "I simply do not remember getting out of bed, being pulled over by
the police, or being cited for three driving infractions," Kennedy said.
Zolpidem, along with the other benzodiazepine-like Z-drugs is a Schedule
IV controlled substance in the USA, according to the Controlled
Substances Act, given its potential for abuse and dependence.
Date-rape drug[edit]
According to the U.S. Drug Enforcement Administration, zolpidem
(Ambien, Stilnox) is quickly overtaking illegal sedatives as the most
common date-rape drug. Perpetrators of sexual assault have used
zolpidem on unsuspecting victims.[63][64]
Usage[edit]
Zolpidem is one of the most common GABA-potentiating sleeping
medications prescribed in the Netherlands, with a total of 582,660
prescriptions dispensed in 2008.[65]
The United States Air Force uses zolpidem as one of the hypnotics
approved as "no-go pills" to help aviators and special duty personnel sleep
in support of mission readiness (the other hypnotics used are temazepam
and zaleplon during war time). "Ground tests" are required prior to
authorization issued to use the medication in an operational situation.[66]
Research[edit]
Zolpidem may provide short-lasting but effective improvement in symptoms
of aphasia present in some survivors of stroke. The mechanism for
improvement in these cases remains unexplained and is the focus of
current research by several groups, to explain how a drug which acts as a
hypnotic-sedative in people with normal brain function, can paradoxically
increase speech ability in people recovering from severe brain injury. Use
of zolpidem for this application remains experimental at this time, and is
not officially approved by any pharmaceutical manufacturers of zolpidem or
medical regulatory agencies worldwide.[67][68][69][70][71]
Zolpidem is being studied to determine if it causes improved
responsiveness or regional cerebral perfusion in patients with persistent
vegetative states.[72][73][74]
References[edit]
1. Jump up ^ Home Office circular 039 / 2003
2. Jump up ^ "Prescribing Information" (PDF). sanofi-aventis. 2007. Retrieved
2011-08-29.
3. Jump up ^ Lemmer B (2007). "The sleep-wake cycle and sleeping pills".
Physiol. Behav. 90 (2–3): 285–93. doi:10.1016/j.physbeh.2006.09.006.
PMID 17049955.
4. ^ Jump up to: a b Rosenberg, RP. (Jan–Mar 2006). "Sleep maintenance
insomnia: strengths and weaknesses of current pharmacologic therapies.".
Ann Clin Psychiatry 18 (1): 49–56. doi:10.1080/10401230500464711.
PMID 16517453.
5. Jump up ^ Patat A; Naef MM, van Gessel E, Forster A, Dubruc C,
Rosenzweig P (October 1994). "Flumazenil antagonizes the central effects
of zolpidem, an imidazopyridine hypnotic". Clin Pharmacol Ther 56 (4):
430–6. doi:10.1038/clpt.1994.157. PMID 7955804.
6. Jump up ^ Wesensten NJ; Balkin TJ, Davis HQ, Belenky GL (September
1995). "Reversal of triazolam- and zolpidem-induced memory impairment
by flumazenil". Psychopharmacology (Berl) 121 (2): 242–9.
doi:10.1007/BF02245635. PMID 8545530.
7. Jump up ^ Depoortere H, Zivkovic B, Lloyd KG, Sanger DJ, Perrault G,
Langer SZ, Bartholini G (1986). "Zolpidem, a novel nonbenzodiazepine
hypnotic. I. Neuropharmacological and behavioral effects". J. Pharmacol.
Exp. Ther. 237 (2): 649–58. PMID 2871178.
8. Jump up ^ US 4382938, Kaplan J-P, George P, "Imidazo[1,2-a] pyridine
derivatives and their application as pharmaceuticals", published 1983-0510, issued 1984-07-17, assigned to Synthelabo
9. Jump up ^ "FDA Approves First Generic Versions of Ambien (Zolpidem
Tartrate) for the Treatment of Insomnia". Retrieved 2010-01-24.
10.
Jump up ^ http://www.guardian.co.uk/science/2012/feb/27/sleepingpills-increase-risk-death-study
11.
Jump up ^ "FDA tells drugmakers to lower doses for Ambien, other
sleeping pills". CBS News. Retrieved 10 January 2013.
12.
Jump up ^
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
http://www.lawyersandsettlements.com/articles/personal_injury/AmbienFDA-Dosing-changes-18721.html#.UZPs8St35cI
Jump up ^ "Ambien". The American Society of Health-System
Pharmacists. Retrieved 3 April 2011.
Jump up ^ Huedo-Medina, TB; Kirsch, I; Middlemass, J; Klonizakis, M;
Siriwardena, AN (2012 Dec 17). "Effectiveness of non-benzodiazepine
hypnotics in treatment of adult insomnia: meta-analysis of data submitted
to the Food and Drug Administration.". BMJ (Clinical research ed.) 345:
e8343. doi:10.1136/bmj.e8343. PMC 3544552. PMID 23248080.
Jump up ^ Yasui M, Kato A, Kanemasa T, Murata S, Nishitomi K, Koike
K, Tai N, Shinohara S, Tokomura M, Horiuchi M, Abe K (2005).
"[Pharmacological profiles of benzodiazepinergic hypnotics and
correlations with receptor subtypes]" [Pharmacological profiles of
benzodiazepinergic hypnotics and correlations with receptor subtypes].
Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of
Psychopharmacology (in Japanese) 25 (3): 143–51. PMID 16045197.
Jump up ^ http://thoughtcatalog.com/2011/an-account-of-sharing-anambien-with-a-girl-i-met-one-week-prior-at-a-party/
Jump up ^ NPS Position Statement: Zolpidem and sleep-related
behaviours (2008). Available at
http://nps.org.au/news_and_media/media_releases/repository/zolpidem_st
ilnox_info_for_prescribers
Jump up ^ Schenck, CH.; Arnulf, I.; Mahowald, MW. (Jun 2007). "Sleep
and Sex: What Can Go Wrong? A Review of the Literature on Sleep
Related Disorders and Abnormal Sexual Behaviors and Experiences".
Sleep 30 (6): 683–702. PMC 1978350. PMID 17580590.
Jump up ^ Dolder CR, Nelson MH (2008). "Hypnosedative-induced
complex behaviours : incidence, mechanisms and management". CNS
Drugs 22 (12): 1021–36. doi:10.2165/0023210-200822120-00005.
PMID 18998740.
Jump up ^ Perchance To ... Eat?
Jump up ^ Vermeeren A (2004). "Residual effects of hypnotics:
epidemiology and clinical implications". CNS Drugs 18 (5): 297–328.
doi:10.2165/00023210-200418050-00003. PMID 15089115.
Jump up ^ Gilmore, Heath (2007-03-11). "Sleeping pill safety under
federal review". the Sydney Morning Herald. Retrieved 2007-03-11.
Jump up ^ "Zolpidem ("Stilnox") – updated information – February
2008". www.tga.gov.au. Retrieved 2009-06-22.
Jump up ^ "Stilnox warnings upgraded" (2008).The Sydney Morning
Herald. Available at http://www.smh.com.au/news/national/stilnox-pillwarnings-upgraded/2008/08/11/1218306743431.html
Jump up ^ Bachl, Matt (2008). "Stilnox blamed for Harbour Bridge
death". nineMSN News. Available at
http://news.ninemsn.com.au/article.aspx?id=381502
Jump up ^ http://www.ncbi.nlm.nih.gov/pubmed/15323600
Jump up ^ http://www.ncbi.nlm.nih.gov/pubmed/8071269
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
Jump up ^ Kirkwood CK (1999). "Management of insomnia". J Am
Pharm Assoc (Wash) 39 (5): 688–96; quiz 713–4. PMID 10533351.
Jump up ^ Petroski RE, Pomeroy JE, Das R (April 2006). "Indiplon is a
high-affinity positive allosteric modulator with selectivity for alpha1 subunitcontaining GABAA receptors" (PDF). J. Pharmacol. Exp. Ther. 317 (1):
369–77. doi:10.1124/jpet.105.096701. PMID 16399882.
Jump up ^ Harter C, Piffl-Boniolo E, Rave-Schwank M (November
1999). "[Development of drug withdrawal delirium after dependence on
zolpidem and zoplicone]" [Development of drug withdrawal delirium after
dependence on zolpidem and zoplicone]. Psychiatr Prax (in German) 26
(6): 309. PMID 10627964.
Jump up ^ "Hypnotic dependence: zolpidem and zopiclone too".
Prescrire Int 10 (51): 15. February 2001. PMID 11503851.
Jump up ^ Sethi PK, Khandelwal DC (February 2005). "Zolpidem at
supratherapeutic doses can cause drug abuse, dependence and
withdrawal seizure" (PDF). J Assoc Physicians India 53: 139–40.
PMID 15847035.
Jump up ^ Quaglio G; Lugoboni F, Fornasiero A, Lechi A, Gerra G,
Mezzelani P (September 2005). "Dependence on zolpidem: two case
reports of detoxification with flumazenil infusion". Int Clin
Psychopharmacol 20 (5): 285–7.
doi:10.1097/01.yic.0000166404.41850.b4. PMID 16096519.
Jump up ^ Lheureux P, Debailleul G, De Witte O, Askenasi R (1990).
"Zolpidem intoxication mimicking narcotic overdose: response to
flumazenil". Human & Experimental Toxicology 9 (2): 105–7.
doi:10.1177/096032719000900209. PMID 2111156.
Jump up ^ Jones AW, Holmgren A, Kugelberg FC. Concentrations of
scheduled prescription drugs in blood of impaired drivers: considerations
for interpreting the results. Ther. Drug Monit. 29: 248–260, 2007.
Jump up ^ Gock SB, Wong SH, Nuwayhid N, Venuti SE, Kelley PD,
Teggatz JR, Jentzen JM. Acute zolpidem overdose—report of two cases.
J. Anal. Toxicol. 23: 559–562, 1999.
Jump up ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man,
9th edition, Biomedical Publications, Seal Beach, CA, 2011, pp. 1836–
1838.
Jump up ^ Gustavsen I, Bramness JG, Skurtveit S, Engeland A, Neutel
I, Mørland J (December 2008). "Road traffic accident risk related to
prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and
nitrazepam". Sleep Med. 9 (8): 818–22. doi:10.1016/j.sleep.2007.11.011.
PMID 18226959.
Jump up ^ "FDA Requires Lower Dosing of Zolpidem". The Medical
Letter on Drugs and Therapeutics (The Medical Letter) 55 (1408): 5.
January 21, 2013. Retrieved April 14, 2013.
Jump up ^ FDA Drug Safety Communication: Risk of next-morning
impairment after use of insomnia drugs; FDA requires lower
recommended doses for certain drugs containing zolpidem (Ambien,
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
Ambien CR, Edluar, and Zolpimist), FDA, January 10, 2013, retrieved April
14, 2013
Jump up ^ Antai-Otong D (August 2006). "The art of prescribing. Risks
and benefits of non-benzodiazepine receptor agonists in the treatment of
acute primary insomnia in older adults". Perspect Psychiatr Care 42 (3):
196–200. doi:10.1111/j.1744-6163.2006.00070.x. PMID 16916422.
Jump up ^ Bain KT (June 2006). "Management of chronic insomnia in
elderly persons". Am J Geriatr Pharmacother 4 (2): 168–92.
doi:10.1016/j.amjopharm.2006.06.006. PMID 16860264.
Jump up ^ Gagliardi GS, Shah AP, Goldstein M, Denua-Rivera S,
Doghramji K, Cohen S, Dimarino AJ (September 2009). "Effect of
zolpidem on the sleep arousal response to nocturnal esophageal acid
exposure". Clin. Gastroenterol. Hepatol. 7 (9): 948–52.
doi:10.1016/j.cgh.2009.04.026. PMID 19426833.
Jump up ^ Drugsdb.eu. "Zolpidem Pregnancy Warnings".
Jump up ^ Salvà P, Costa J (September 1995). "Clinical
pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic
implications". Clin Pharmacokinet 29 (3): 142–53. doi:10.2165/00003088199529030-00002. PMID 8521677.
Jump up ^ Pritchett DB, Seeburg PH (1990). "Gamma-aminobutyric
acidA receptor alpha 5-subunit creates novel type II benzodiazepine
receptor pharmacology". J. Neurochem. 54 (5): 1802–4.
doi:10.1111/j.1471-4159.1990.tb01237.x. PMID 2157817.
Jump up ^ Smith, AJ.; Alder, L.; Silk, J.; Adkins, C.; Fletcher, AE.;
Scales, T.; Kerby, J.; Marshall, G. et al. (May 2001). "Effect of alpha
subunit on allosteric modulation of ion channel function in stably
expressed human recombinant gamma-aminobutyric acid(A) receptors
determined using (36)Cl ion flux" (PDF). Mol Pharmacol 59 (5): 1108–18.
PMID 11306694.
Jump up ^ Rowlett JK, Woolverton WL (November 1996). "Assessment
of benzodiazepine receptor heterogeneity in vivo: apparent pA2 and pKB
analyses from behavioral studies". Psychopharmacology (Berl.) 128 (1):
1–16. doi:10.1007/s002130050103. PMID 8944400.
Jump up ^ Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS,
Whiting PJ (1996). "Functional characterization of human gammaaminobutyric acidA receptors containing the alpha 4 subunit". Mol.
Pharmacol. 50 (3): 670–8. PMID 8794909.
Jump up ^ Perrais D, Ropert N (1999). "Effect of zolpidem on miniature
IPSCs and occupancy of postsynaptic GABAA receptors in central
synapses". J. Neurosci. 19 (2): 578–88. PMID 9880578.
Jump up ^ Noguchi H, Kitazumi K, Mori M, Shiba T (2004).
"Electroencephalographic properties of zaleplon, a non-benzodiazepine
sedative/hypnotic, in rats". J. Pharmacol. Sci. 94 (3): 246–51.
doi:10.1254/jphs.94.246. PMID 15037809. "WARNING: The reference
indicates that zaleplon-Sonata, not zolpidem, increases Slow-wave sleep"
Jump up ^ Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
(2004). "Comparative efficacy of newer hypnotic drugs for the short-term
management of insomnia: a systematic review and meta-analysis".
Human psychopharmacology 19 (5): 305–22. doi:10.1002/hup.594.
PMID 15252823.
Jump up ^ Hulhoven, R.; Desager, J. P.; Harvengt, C.; Hermann, P.;
Guillet, P.; Thiercelin, J. F. (1988). "Lack of interaction between zolpidem
and H2 antagonists, cimetidine and ranitidine". International journal of
clinical pharmacology research 8 (6): 471–476. PMID 3253224.
Jump up ^ Wang JS, DeVane CL (2003). "Pharmacokinetics and drug
interactions of the sedative hypnotics" (PDF). Psychopharmacol Bull 37
(1): 10–29. doi:10.1007/BF01990373. PMID 14561946.
Jump up ^ Hulhoven, R.; Desager, J. P.; Harvengt, C.; Hermann, P.;
Guillet, P.; Thiercelin, J. F. (1988). "Lack of interaction between zolpidem
and H2 antagonists, cimetidine and ranitidine". International journal of
clinical pharmacology research 8 (6): 471–476. PMID 3253224.
Jump up ^ Griffiths RR, Johnson MW (2005). "Relative abuse liability of
hypnotic drugs: a conceptual framework and algorithm for differentiating
among compounds". J Clin Psychiatry. 66 Suppl 9: 31–41.
PMID 16336040.
Jump up ^ Barrero-Hernández FJ, Ruiz-Veguilla M, López-López MI,
Casado-Torres A (2002). "[Epileptic seizures as a sign of abstinence from
chronic consumption of zolpidem]" [Epileptic seizures as a sign of
abstinence from chronic consumption of zolpidem]. Rev Neurol (in
Spanish; Castilian) 34 (3): 253–6. PMID 12022074.
Jump up ^ Cubała WJ, Landowski J (2007). "Seizure following sudden
zolpidem withdrawal". Prog. Neuropsychopharmacol. Biol. Psychiatry 31
(2): 539–40. doi:10.1016/j.pnpbp.2006.07.009. PMID 16950552.
Jump up ^ [1], additional text.
Jump up ^ "ksl.com – Ambien Abuse on Rise Among Teens".
www.ksl.com. Retrieved 2009-06-22.
Jump up ^ Jones AW, Holmgren A, Kugelberg FC (2007).
"Concentrations of scheduled prescription drugs in blood of impaired
drivers: considerations for interpreting the results". Therapeutic drug
monitoring 29 (2): 248–60. doi:10.1097/FTD.0b013e31803d3c04.
PMID 17417081.
Jump up ^ Kennedy To Enter Drug Rehab After Car Crash;
Congressman Wrecked Car Near Capitol
Jump up ^ Kintz, P. (2007). "Bioanalytical procedures for detection of
chemical agents in hair in the case of drug-facilitated crimes". Analytical
and Bioanalytical Chemistry 388 (7): 1467–1474. doi:10.1007/s00216007-1209-z. PMID 17340077. edit
Jump up ^ Madea, B.; Musshoff, F. (2009). "Knock-out drugs: their
prevalence, modes of action, and means of detection". Deutsches
Arzteblatt international 106 (20): 341–347. doi:10.3238/arztebl.2009.0341.
PMC 2689633. PMID 19547737. edit
Jump up ^ http://www.gipdatabank.nl/
66.
67.
68.
69.
70.
71.
72.
73.
74.
Jump up ^ http://www.epublishing.af.mil/shared/media/epubs/AFSOCI48-101.pdf
Jump up ^ Clauss R, Nel W (2006). "Drug induced arousal from the
permanent vegetative state". NeuroRehabilitation 21 (1): 23–8.
PMID 16720934.
Jump up ^ Whyte J, Myers R (May 2009). "Incidence of clinically
significant responses to zolpidem among patients with disorders of
consciousness: a preliminary placebo controlled trial". American Journal of
Physical Medicine & Rehabilitation / Association of Academic Physiatrists
88 (5): 410–8. doi:10.1097/PHM.0b013e3181a0e3a0. PMID 19620954.
Jump up ^ Hall SD, Yamawaki N, Fisher AE, Clauss RP, Woodhall GL,
Stanford IM (April 2010). "GABA(A) alpha-1 subunit mediated
desynchronization of elevated low frequency oscillations alleviates specific
dysfunction in stroke--a case report". Clinical Neurophysiology : Official
Journal of the International Federation of Clinical Neurophysiology 121 (4):
549–55. doi:10.1016/j.clinph.2009.11.084. PMID 20097125.
Jump up ^ Nyakale NE, Clauss RP, Nel W, Sathekge M (2010).
"Clinical and brain SPECT scan response to zolpidem in patients after
brain damage". Arzneimittel-Forschung 60 (4): 177–81. doi:10.1055/s0031-1296269. PMID 20486466.
Jump up ^ Machado C, Estévez M, Pérez-Nellar J, Gutiérrez J,
Rodríguez R, Carballo M, Chinchilla M, Machado A, Portela L, GarcíaRoca MC, Beltrán C (March 2011). "Autonomic, EEG, and behavioral
arousal signs in a PVS case after Zolpidem intake". The Canadian Journal
of Neurological Sciences. Le Journal Canadien Des Sciences
Neurologiques 38 (2): 341–4. PMID 21320843.
Jump up ^ Snyman, N.; Egan, J. R.; London, K.; Howman-Giles, R.;
Gill, D.; Gillis, J.; Scheinberg, A. (2011). "Zolpidem for Persistent
Vegetative State - A Placebo-Controlled Trial in Pediatrics".
Neuropediatrics 41 (5): 223–227. doi:10.1055/s-0030-1269893.
PMID 21210338. edit
Jump up ^ Whyte, J.; Myers, R. (2009). "Incidence of Clinically
Significant Responses to Zolpidem Among Patients with Disorders of
Consciousness". American Journal of Physical Medicine & Rehabilitation
88 (5): 410–418. doi:10.1097/PHM.0b013e3181a0e3a0.
PMID 19620954. edit
Jump up ^ A Drug That Wakes the Near Dead The New York Times.
December 1, 2011.
Further reading[edit]
• Joel Lamoure RPh. BScPhm.,FASCP. "How Is Zolpidem Dependence
Managed?". Medscape Pharmacists Ask the Expert. WebMD. Retrieved
2010-03-05.
• "Prescription Sleep Aid AMBIEN CR". Sanofi-Aventis. Retrieved 2009-05-21.
"Ambien CR official website"
• "Ambien Cr (zolpidem tartrate) Tablet, Coated". DailyMed. U.S. National
Library of Medicine, National Institutes of Health, Health & Human
Services. Retrieved 2009-05-21.
• "Zolpidem (Ambien)". The Vaults of Erowid. 2007-07-19. Retrieved 2009-0521.
• Angelettie L, Kelley-Soderholm E. "Ambien Abuse". Mental Health Site.
BellaOnline, Minerva WebWorks LLC. Retrieved 2009-05-21.
• U.S. National Library of Medicine: Drug Information Portal – Zolpidem
External links[edit]
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