Zaleplon
Encyclopedia
Zaleplon is a sedative
/hypnotic
, mainly used for insomnia
. It is a nonbenzodiazepine
hypnotic
from the pyrazolopyrimidine
class. In terms of adverse effects zaleplon appears to offer little improvement compared to both benzodiazepine
s and other non-benzodiazepine Z-drug
s.
Sonata (US) is manufactured by King Pharm. of Bristol, TN; Starnoc has been discontinued in Canada. It's usually prescribed privately (rarely) in the United Kingdom
; with Zopiclone
being the preferred Z-Drug by the NHS
.
Zaleplon is also effective in the treatment of middle of the night insomnia without causing residual hangover effects.
Zaleplon has advantages over benzodiazepines in that it does not disrupt sleep architecture
unlike benzodiazepines which whilst inducing sleep actually worsen the quality of it.
Zaleplon may cause
day-time drowsiness, dizziness
, headache
.
Zaleplon is not addictive, and does not cause addiction and drug dependence is unlikely. Stopping this medication suddenly after prolonged or frequent use usually does not cause withdrawal effects such as mood changes, anxiety, restlessness, or rebound insomnia unlike other drugs such as Ambien.
Some evidence suggests that Zaleplon tolerance and rebound effects may be less frequent than with other nonbenzodiazepine Z-drugs in its class.
(including zaleplon) sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, 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. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.
properties. The ultra short half-life gives zaleplon a unique advantage over other hypnotics because of its lack of next day residual effects on driving and other performance related skills. Unlike non-selective benzodiazepine
drugs and zopiclone which distort the sleep pattern zaleplon appears to induce sleep without disrupting the natural sleep architecture.
A meta-analysis
of randomised controlled clinical trials which compared benzodiazepines against Zaleplon or other Z Drugs such as zolpidem
and zopiclone
, has found that there are few clear and consistent differences between Zaleplon and the benzodiazepines in terms of sleep onset latency
, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia and daytime alertness.
Zaleplon has a pharmacological profile similar to benzodiazepines, that is characterized by an increase in SWDS with rapid onset of hypnotic action. Zaleplon is a full agonist for the benzodiazepine
α1 receptor located on the GABAA receptor ionophore complex in the brain, with lower affinity for the α2 and α3 subtypes. It selectively enhances the action of GABA similar to but more selectively than benzodiazepines. Zaleplon, although not benzodiazepine-like in chemical structure induces sedative-hypnotic, anticonvulsant and anticonflict effects via its binding to the central nervous system (CNS) type benzodiazepine receptors. The elimination half-life of zaleplon is 1 hour. Absorption is rapid. Zaleplon can be classed as an ultra short acting sedative hypnotic drug for the treatment of insomnia characterised by difficulty in falling asleep. Zaleplon increases EEG
power density in the delta frequency band and a decrease in the energy of the theta frequency band. In tests on rabbits zaleplon shows drowsy pattern of spontaneous EEG characterized by high-voltage slow waves and desynchronization of hippocampal theta waves and an increase in the energy of the delta frequency band on the spectral analysis of the electroencephalogram.
in water as well as low solubility in alcohol
and propylene glycol
. It has a partition coefficient in octanol/water that is constant (log PC = 1.23) when the pH
range is between 1 and 7.
, and its half-life can be affected by substances which inhibit or induce aldehyde oxidase. Taken orally, zaleplon reaches full concentration in approximately one hour. It is extensively metabolised, into 5-oxo-zaleplon and 5-oxo-desethylzaleplon (the latter via desethylzaleplon), with less than 1% of it excreted intact in urine.
, rifampicin
and thioridazine
cause interactions with zaleplon.
) to induce effects faster.
The effects of Zaleplon are similar to those of many other benzodiazepines but the fast-acting nature and short half-life of the chemical mean that high dosages set on much more quickly and last for short periods of time (usually from 45 to 60 minutes). Insufflating the drug causes effects to happen even more quickly, and last for even shorter periods of time, with some loss of yield as Zaleplon is not entirely water soluble. A common effect of Zaleplon abuse is the occurrence of hallucinations, commonly involving perceptions of nonexistent creatures. Anterograde amnesia
is very common, and can cause one to lose track of the amount of Zaleplon already ingested, causing them to ingest more than originally planned.
Sedative
A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....
/hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
, mainly used for insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. It is a nonbenzodiazepine
Nonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
hypnotic
Hypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
from the pyrazolopyrimidine
Pyrazolopyrimidine
Pyrazolopyrimidine is a heterocyclic chemical compound with the molecular formula C6H5N3. It forms the central core of a variety of more complex chemical compounds including some pharmaceuticals and pesticides.-Pharmaceuticals:...
class. In terms of adverse effects zaleplon appears to offer little improvement compared to both benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s and other non-benzodiazepine Z-drug
Z-drug
Z-drugs are a group of nonbenzodiazepine drugs with effects similar to benzodiazepines which are used in the treatment of insomnia, and whose names mostly start with the letter "Z". Some Z drugs may have advantages over benzodiazepines...
s.
Sonata (US) is manufactured by King Pharm. of Bristol, TN; Starnoc has been discontinued in Canada. It's usually prescribed privately (rarely) in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
; with Zopiclone
Zopiclone
Zopiclone is a non-benzodiazepine hypnotic agent used in the treatment of insomnia. In the United States, zopiclone is not commercially available, although its active stereoisomer, eszopiclone, is sold under the name Lunesta...
being the preferred Z-Drug by the NHS
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
.
Clinical uses
Zaleplon is effective in the treatment of insomnia where difficulty in falling asleep is the primary complaint. Zaleplon, unlike many other hypnotic drugs, does not interfere with sleep architecture and can be administered for up to long term without the risk of dependence or addiction upon discontinuation.Zaleplon is also effective in the treatment of middle of the night insomnia without causing residual hangover effects.
Zaleplon has advantages over benzodiazepines in that it does not disrupt sleep architecture
Sleep architecture
Sleep architecture describes the structure and pattern of sleep and encompasses several variables. Sleep quotas refer to the amount of time spent in REM and NREM sleep. Sleep duration is the total time spent asleep in a 24 hour period. The duration of a NREM-REM cycle is also an important aspect...
unlike benzodiazepines which whilst inducing sleep actually worsen the quality of it.
Side-effects
The side effects of zaleplon are similar to the side effects of benzodiazepines, although with less next-day sedation, and in two studies Zaleplon use was found to not cause an increase in road traffic accidents as compared to other hypnotics currently on the market.Zaleplon may cause
day-time drowsiness, dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
.
Zaleplon is not addictive, and does not cause addiction and drug dependence is unlikely. Stopping this medication suddenly after prolonged or frequent use usually does not cause withdrawal effects such as mood changes, anxiety, restlessness, or rebound insomnia unlike other drugs such as Ambien.
Some evidence suggests that Zaleplon tolerance and rebound effects may be less frequent than with other nonbenzodiazepine Z-drugs in its class.
Special precautions
The elderly are more sensitive to the adverse effects of zaleplon such as cognitive side effects. Zaleplon may increase the risk of falls in the elderly. It should not be used in pregnancy and lactation, in patients with a history of alcohol or drug abuse, psychotic illness or depression.Elderly
An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines, the nonbenzodiazepineNonbenzodiazepine
The nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
(including zaleplon) sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, 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
Anterograde amnesia
Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...
), 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. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.
Pharmacology
Zaleplon selectively binds with high efficacy to the benzodiazepine site (ω1) on the α1 containing GABAA receptors which produces its therapeutic hypnoticHypnotic
Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...
properties. The ultra short half-life gives zaleplon a unique advantage over other hypnotics because of its lack of next day residual effects on driving and other performance related skills. Unlike non-selective benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
drugs and zopiclone which distort the sleep pattern zaleplon appears to induce sleep without disrupting the natural sleep architecture.
A meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
of randomised controlled clinical trials which compared benzodiazepines against Zaleplon or other Z Drugs such as zolpidem
Zolpidem
Zolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
and zopiclone
Zopiclone
Zopiclone is a non-benzodiazepine hypnotic agent used in the treatment of insomnia. In the United States, zopiclone is not commercially available, although its active stereoisomer, eszopiclone, is sold under the name Lunesta...
, has found that there are few clear and consistent differences between Zaleplon and the benzodiazepines in terms of sleep onset latency
Sleep onset latency
In sleep science, sleep onset latency is the length of time that it takes to accomplish the transition from full wakefulness to sleep, normally to the lightest of the non-REM sleep stages.-Sleep latency studies:...
, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia and daytime alertness.
Zaleplon has a pharmacological profile similar to benzodiazepines, that is characterized by an increase in SWDS with rapid onset of hypnotic action. Zaleplon is a full agonist for the benzodiazepine
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
α1 receptor located on the GABAA receptor ionophore complex in the brain, with lower affinity for the α2 and α3 subtypes. It selectively enhances the action of GABA similar to but more selectively than benzodiazepines. Zaleplon, although not benzodiazepine-like in chemical structure induces sedative-hypnotic, anticonvulsant and anticonflict effects via its binding to the central nervous system (CNS) type benzodiazepine receptors. The elimination half-life of zaleplon is 1 hour. Absorption is rapid. Zaleplon can be classed as an ultra short acting sedative hypnotic drug for the treatment of insomnia characterised by difficulty in falling asleep. Zaleplon increases EEG
EEG
EEG commonly refers to electroencephalography, a measurement of the electrical activity of the brain.EEG may also refer to:* Emperor Entertainment Group, a Hong Kong-based entertainment company...
power density in the delta frequency band and a decrease in the energy of the theta frequency band. In tests on rabbits zaleplon shows drowsy pattern of spontaneous EEG characterized by high-voltage slow waves and desynchronization of hippocampal theta waves and an increase in the energy of the delta frequency band on the spectral analysis of the electroencephalogram.
Chemistry
Pure zaleplon in its solid state is a white to off-white powder that has very low solubilitySolubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
in water as well as low solubility in alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
and propylene glycol
Propylene glycol
Propylene glycol, also called 1,2-propanediol or propane-1,2-diol, is an organic compound with formula C3H8O2 or HO-CH2-CHOH-CH3...
. It has a partition coefficient in octanol/water that is constant (log PC = 1.23) when the pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
range is between 1 and 7.
Pharmacokinetics
Zaleplon is primarily metabolised by aldehyde oxidaseAldehyde oxidase
Aldehyde oxidase is an enzyme which generates carboxylic acids from aldehydes. It catalyzes the conversion of an aldehyde in the presence of oxygen and water to an acid and hydrogen peroxide.* an aldehyde + H2O + O2 a carboxylate + H2O2 + H+...
, and its half-life can be affected by substances which inhibit or induce aldehyde oxidase. Taken orally, zaleplon reaches full concentration in approximately one hour. It is extensively metabolised, into 5-oxo-zaleplon and 5-oxo-desethylzaleplon (the latter via desethylzaleplon), with less than 1% of it excreted intact in urine.
Interactions
CimetidineCimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
, rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
and thioridazine
Thioridazine
Thioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis...
cause interactions with zaleplon.
Recreational use
Zaleplon (Sonata) has a relatively high potential to be abused. Often this use involves a different delivery method (insufflatingInsufflation (medicine)
Insufflation is the practice of inhaling a substance. Insufflation has limited medical use, but is a common route of administration with many respiratory drugs used to treat conditions in the lungs and paranasal sinus .The technique is common for many recreational drugs and is also used for some...
) to induce effects faster.
Anterograde amnesia
Anterograde amnesia is a loss of the ability to create new memories after the event that caused the amnesia, leading to a partial or complete inability to recall the recent past, while long-term memories from before the event remain intact. This is in contrast to retrograde amnesia, where memories...
is very common, and can cause one to lose track of the amount of Zaleplon already ingested, causing them to ingest more than originally planned.
See also
- NonbenzodiazepineNonbenzodiazepineThe nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs pharmacologically resembling the benzodiazepines, with similar benefits, side effects and risks, despite having dissimilar or entirely different chemical structures.-Classes:There are currently three...
- Z-drugs (excluding Zaleplon (Sonata))
- ZolpidemZolpidemZolpidem is a prescription medication used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic of the imidazopyridine class that potentiates gamma-aminobutyric acid , an inhibitory neurotransmitter, by binding to GABAA...
(Ambien) - ZopicloneZopicloneZopiclone is a non-benzodiazepine hypnotic agent used in the treatment of insomnia. In the United States, zopiclone is not commercially available, although its active stereoisomer, eszopiclone, is sold under the name Lunesta...
(Imovane) - EszopicloneEszopicloneEszopiclone, marketed by Sepracor under the brand-name Lunesta, is a nonbenzodiazepine hypnotic used as a treatment for insomnia. Eszopiclone is the active dextrorotatory stereoisomer of zopiclone, and belongs to the class of drugs known as cyclopyrrolones.Eszopiclone is a short acting...
(Lunesta)