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sleep inducing (同)soporiferous, somniferous, somnific, hypnogogic, hypnagogic
a drug that induces sleep (同)hypnotic

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/24 10:08:12」(JST)

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Stilnoct (zolpidem) tablets, a common hypnotic

Hypnotic (from Greek Hypnos, sleep) or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep^[1] and to be used in the treatment of insomnia (sleeplessness), or surgical anesthesia.^{[note 1]}

This group is related to sedatives. Whereas the term sedative describes drugs that serve to calm or relieve anxiety, the term hypnotic generally describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from anxiolysis to loss of consciousness) they are often referred to collectively as sedative-hypnotic drugs.^[2]

Hypnotic drugs are regularly prescribed for insomnia and other sleep disorders, with over 95% of insomnia patients being prescribed hypnotics in some countries.^[3] Many hypnotic drugs are habit-forming and, due to a large number of factors known to disturb the human sleep pattern, a physician may instead recommend changes in the environment before and during sleep, better sleep hygiene, and the avoidance of caffeine or other stimulating substances before prescribing medication for sleep. When prescribed, hypnotic medication should be used for the shortest period of time possible.^[4]

Most hypnotics prescribed today are either benzodiazepines or nonbenzodiazepines.^{[medical citation needed]} Among individuals with sleep disorders, 13.7% are taking or prescribed nonbenzodiazepines, while 10.8% are taking benzodiazepines, as of 2010.^[5] Early classes of drugs, such as barbiturates, have fallen out of use in most practices but are still prescribed for some patients. In children, prescribing hypnotics is not yet acceptable unless used to treat night terrors or somnambulism.^[6] Elderly people are more sensitive to potential side effects of daytime fatigue and cognitive impairments, and a meta-analysis found that the risks generally outweigh any marginal benefits of hypnotics in the elderly.^[7] A review of the literature regarding benzodiazepine hypnotics and Z-drugs concluded that these drugs can have adverse effects, such as dependence and accidents, and that optimal treatment uses the lowest effective dose for the shortest therapeutic time period, with gradual discontinuation in order to improve health without worsening of sleep.^[8]

Falling outside of the above-mentioned categories, the neuro-hormone melatonin has a hypnotic function.^[9]

1 History
2 Types
- 2.1 Barbiturates
- 2.2 Quinazolinones
- 2.3 Benzodiazepines
- 2.4 Nonbenzodiazepines
- 2.5 Others
  - 2.5.1 Melatonin
  - 2.5.2 Antihistamines
  - 2.5.3 Antidepressants
  - 2.5.4 Antipsychotics
  - 2.5.5 Miscellaneous Others
3 See also
4 Notes
5 References
6 Further reading
7 External links

History

Hypnotica was a class of somniferous drugs and substances tested in medicine of the 1890s and later, including: Urethan, Acetal, Methylal, Sulfonal, Paraldehyd, Amylenhydrate, Hypnon, Chloralurethan and Ohloralamid or Chloralimid.^[10]

Research about using medications to treat insomnia evolved throughout the last half of the 20th century. Treatment for insomnia in psychiatry dates back to 1869 when chloral hydrate was first used as a soporific.^[11] Barbiturates emerged as the first class of drugs that emerged in the early 1900s,^[12] after which chemical substitution allowed derivative compounds. Although the best drug family at the time (less toxic and with fewer side effects) they were dangerous in overdose.^[13]^[14]^[15]

During the 1970s, quinazolinones^{[citation needed]} and benzodiazepines were introduced as safer alternatives to replace barbiturates; by the late 1970s benzodiazepines emerged as the safer drug.^[11]

Benzodiazepines are not without their drawbacks; substance dependence is possible, and deaths from overdoses sometimes occur, especially in combination with alcohol and/or other depressants. Questions have been raised as to whether they disturb sleep architecture.^[16]

Nonbenzodiazepines are the most recent development (1990s–present). Although it's clear that they are less toxic than their predecessors, barbiturates, comparative efficacy over benzodiazepines have not been established. Without longitudinal studies, it is hard to determine; however some psychiatrists recommend these drugs, citing research suggesting they are equally potent with less potential for abuse.^[17]

Other sleep remedies that may be considered "sedative-hypnotics" exist; psychiatrists will sometimes prescribe medicines off-label if they have sedating effects. Examples of these include mirtazapine (an antidepressant), clonidine (generally prescribed to regulate blood pressure), quetiapine (an antipsychotic), and the over-the-counter sleep aid diphenhydramine (Benadryl – an antihistamine). Off-label sleep remedies are particularly useful when first-line treatment is unsuccessful or deemed unsafe (for example, in patients with a history of substance abuse).

Types

Barbiturates

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, hypnotics, and anticonvulsants. Barbiturates also have analgesic effects; however, these effects are somewhat weak, preventing barbiturates from being used in surgery in the absence of other analgesics. They have dependence liability, both physical and psychological. Barbiturates have now largely been replaced by benzodiazepines in routine medical practice – for example, in the treatment of anxiety and insomnia – mainly because benzodiazepines are significantly less dangerous in overdose. However, barbiturates are still used in general anesthesia, for epilepsy, and assisted suicide. Barbiturates are derivatives of barbituric acid.

The principal mechanism of action of barbiturates is believed to be positive allosteric modulation of GABA_A receptors.^[18]

Examples include amobarbital, pentobarbital, phenobarbital, secobarbital, and sodium thiopental.

Quinazolinones

Quinazolinones are also a class of drugs which function as hypnotic/sedatives that contain a 4-quinazolinone core. Their use has also been proposed in the treatment of cancer.^[19]

Examples of quinazolinones include cloroqualone, diproqualone, etaqualone (Aolan, Athinazone, Ethinazone), mebroqualone, mecloqualone (Nubarene, Casfen), and methaqualone (Quaalude).

Benzodiazepines

Benzodiazepines can be useful for short-term treatment of insomnia. Their use beyond 2 to 4 weeks is not recommended due to the risk of dependence. It is preferred that benzodiazepines be taken intermittently and at the lowest effective dose. They improve sleep-related problems by shortening the time spent in bed before falling asleep, prolonging the sleep time, and, in general, reducing wakefulness.^[20]^[21] Like alcohol, benzodiazepines are commonly used to treat insomnia in the short-term (both prescribed and self-medicated), but worsen sleep in the long-term. While benzodiazepines can put people to sleep (i.e., inhibit NREM stage 1 and 2 sleep), while asleep, the drugs disrupt sleep architecture: decreasing sleep time, delaying time to REM sleep, and decreasing deep slow-wave sleep (the most restorative part of sleep for both energy and mood).^[22]^[23]^[24] This can directly and indirectly worsen other psychiatric symptoms such as depression, anxiety and irritability.^[25]^[26]

Other drawbacks of hypnotics, including benzodiazepines, are possible tolerance to their effects, rebound insomnia, and reduced slow-wave sleep and a withdrawal period typified by rebound insomnia and a prolonged period of anxiety and agitation.^[27]^[28] The list of benzodiazepines approved for the treatment of insomnia is fairly similar among most countries, but which benzodiazepines are officially designated as first-line hypnotics prescribed for the treatment of insomnia can vary distinctly between countries.^[21] Longer-acting benzodiazepines such as nitrazepam and diazepam have residual effects that may persist into the next day and are, in general, not recommended.^[20]

It is not clear as to whether the new nonbenzodiazepine hypnotics (Z-drugs) are better than the short-acting benzodiazepines. The efficacy of these two groups of medications is similar.^[20]^[28] According to the US Agency for Healthcare Research and Quality, indirect comparison indicates that side-effects from benzodiazepines may be about twice as frequent as from nonbenzodiazepines.^[28] Some experts suggest using nonbenzodiazepines preferentially as a first-line long-term treatment of insomnia.^[21] However, the UK National Institute for Health and Clinical Excellence (NICE) did not find any convincing evidence in favor of Z-drugs. A NICE review pointed out that short-acting Z-drugs were inappropriately compared in clinical trials with long-acting benzodiazepines. There have been no trials comparing short-acting Z-drugs with appropriate doses of short-acting benzodiazepines. Based on this, NICE recommended choosing the hypnotic based on cost and the patient's preference.^[20]

Older adults should not use benzodiazepines to treat insomnia unless other treatments have failed to be effective.^[29] When benzodiazepines are used, patients, their caretakers, and their physician should discuss the increased risk of harms, including evidence which shows twice the incidence of traffic collisions among driving patients as well as falls and hip fracture for all older patients.^[3]^[29]

Their mechanism of action is primarily at GABA_A receptors.^[30]

Nonbenzodiazepines

Nonbenzodiazepines are a class of psychoactive drugs that are very "benzodiazepine-like" in nature. Nonbenzodiazepines pharmacodynamics are almost entirely the same as benzodiazepine drugs and therefore employ similar benefits, side-effects, and risks. Nonbenzodiazepines, however, have dissimilar or entirely different chemical structures, and therefore are unrelated to benzodiazepines on a molecular level.^[17]^[31]

Examples include zopiclone (Imovane, Zimovane), eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Stilnox, Stilnoct).

Research on nonbenzodiazepines is new and conflicting. A review by a team of researchers suggests the use of these drugs for people that have trouble falling asleep but not staying asleep,^{[note 2]} as next-day impairments were minimal.^[32] The team noted that the safety of these drugs had been established, but called for more research into their long-term effectiveness in treating insomnia. Other evidence suggests that tolerance to nonbenzodiazepines may be slower to develop than with benzodiazepines.^{[not in citation given]} A different team was more skeptical, finding little benefit over benzodiazepines.^[33]

Others

Melatonin

Melatonin, the hormone produced in the pineal gland in the brain and secreted in dim light and darkness, among its other functions, promotes sleep in diurnal mammals.^[34] Due to its hypnotic properties, it is available on prescription in many countries and is over-the-counter in others. A timed-release version, trade name Circadin®, was approved in 2007 in Europe (EU) for use as a treatment for primary insomnia.

At the beginning of the 21st century, several melatonin receptor agonists that bind to and activate melatonin receptors were developed. These analogues, prescribed for several sleep disorders, include ramelteon, agomelatine, TIK-301 and tasimelteon. Ramelteon (Rozerem®) was approved for treatment of insomnia in the US in 2005. In 2009 agomelatine (Valdoxan®, Melitor®, Thymanax®), primarily used for depression, was approved in Europe. Both TIK-301 (in 2004) and tasimelteon (Hetlioz®) ten years later were approved in the US for the circadian rhythm sleep disorder non-24-hour sleep–wake disorder in totally blind individuals.

Antihistamines

In common use, the term antihistamine refers only to compounds that inhibit action at the H₁ receptor (and not H₂, etc.).

Clinically, H₁ antagonists are used to treat certain allergies. Sedation is a common side-effect, and some H₁ antagonists, such as diphenhydramine (Benadryl) and doxylamine, are also used to treat insomnia.

Second-generation antihistamines cross the blood–brain barrier to a much lower degree than the first ones.^{[medical citation needed]} This results in their primarily affecting peripheral histamine receptors, and therefore having a much lower sedative effect. High doses can still induce the central nervous system effect of drowsiness.

Antidepressants

Some antidepressants have sedating effects. Some may increase actual quality of sleep (biologically) in contrast to Benzodiazepines that decrease quality.

Examples include:

Serotonin antagonists and reuptake inhibitors

Trazodone^[35]

Tricyclic antidepressants

Amitriptyline^[36]
Doxepin^[37]
Trimipramine^[38]

Tetracyclic antidepressants

Mianserin^[39]
Mirtazapine^[40]^[41]

Examples include:

Selective serotonin reuptake inhibitors
Serotonin–norepinephrine reuptake inhibitors
Norepinephrine reuptake inhibitors

Antipsychotics

Examples of antipsychotics with sedation as a side effect:^[42]

First-generation

Chlorpromazine

Second-generation

Clozapine
Olanzapine
Quetiapine
Risperidone
Zotepine

Miscellaneous Others

Alpha-adrenergic agonist

Clonidine
Guanfacine

Cannabinoids

Cannabidiol
Tetrahydrocannabinol

Orexin receptor antagonist

Suvorexant

Gabapentinoids

Pregabalin
Gabapentin
Phenibut
Imagabalin

Notes

^ When used in anesthesia to produce and maintain unconsciousness, "sleep" is metaphorical as there are no regular sleep stages or cyclical natural states; patients rarely recover from anesthesia feeling refreshed and with renewed energy.
^ Because the drugs have a shorter elimination half life they are metabolized more quickly: nonbenzodiazepines zaleplon and zolpidem have a half life of 1 and 2 hours (respectively); for comparison the benzodiazepine clonazepam has a half life of about 30 hours. This makes the drug suitable for sleep-onset difficulty, but the team noted sustained sleep efficacy was not clear.

References

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External links

The dictionary definition of hypnotic at Wiktionary
Sleeping pills overview

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Differential regulation of calcium signalling pathways by components of Piper methysticum ('Awa).

Shimoda LM1, Showman A, Baker JD, Lange I, Koomoa DL, Stokes AJ, Borris RP, Turner H.
Phytotherapy research : PTR.Phytother Res.2015 Apr;29(4):582-90. doi: 10.1002/ptr.5291. Epub 2015 Jan 30.
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Hill AJ1, Mansfield R1, Lopez JM1, Raizen DM2, Van Buskirk C3.
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Japanese Journal

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NAID 130004475252

2, 3, 4-トリメトキシ-1-プロペニルベンゼンの新合成

藤田治重 [他],山下正太郎
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… 2, 3, 4-Trimethoxy-1-propenylbenzene, one of soporific and a hypotensive anesthetics, is synthesized from pyrogallol through 4 steps and in good overall yield. …
NAID 130000925321

睡眠時聴性瞳孔反応による他覚的聴力測定の研究

佐々木治夫
日本耳鼻咽喉科学会会報 65(8), 998-1011, 1962
… As soporific, mintal (3-5mg/kg injected in muscles) was used in almost all the cases.2) The cochleo-pupillar responses appear most distinctly when the examinees' sleep is very light and also immediately after they fell into sleep.3) On the ears of normal hearing, 82.5% of them response at 40-70db. …
NAID 130000802620

THE EFFECTS OF CHLORPROMAZINE ON CEREBRAL CIRCULATION AND METABOLISM

AIZAWA TOYOZO,GOTO YUICHIRO,TAZAKI YOSHIAKI,HAMAYA SHOICHI,MAKINO KOKI
The Keio Journal of Medicine 5(4), 205-213, 1956
… Cerebral circulatory measurements were made using the nitrous oxide method in six patients before and after administration of chlorpromazine, and the changes of cerebral hemodynamics, gaseous and glucose metabolism of brain and of electrolyte in hypotensive and soporific state by this drug were studied. …
NAID 130000879414

Related Pictures

soporific sojourns | Flickr - Photo Soporific – Wacky Word Wednesday Soporific', myfather's yacht - Greece 1983 Use of the soporific sponge in 13th Soporific female elephant seal. is soporific,” Beatrix Potter wrote soporific on Tumblr

★リンクテーブル★

リンク元

「入眠薬」

　　[★]

英: drug for sleep induction
英: soporific
同: 睡眠導入薬

[2] When used in anesthesia to produce and maintain unconsciousness, "sleep" is metaphorical as there are no regular sleep stages or cyclical natural states; patients rarely recover from anesthesia feeling refreshed and with renewed energy.

[33] Because the drugs have a shorter elimination half life they are metabolized more quickly: nonbenzodiazepines zaleplon and zolpidem have a half life of 1 and 2 hours (respectively); for comparison the benzodiazepine clonazepam has a half life of about 30 hours. This makes the drug suitable for sleep-onset difficulty, but the team noted sustained sleep efficacy was not clear.

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