Zaleplon

Systematic (IUPAC) name
N-(3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N- ethylacetamide
Clinical data
Trade names	Sonata
AHFS/Drugs.com	monograph
MedlinePlus	a601251
Pregnancy cat.	C (US)
Legal status	Schedule IV (US)
Routes	Oral
Pharmacokinetic data
Bioavailability	30% (oral)
Metabolism	Hepatic
Half-life	1 hour
Excretion	Renal
Identifiers
CAS number	151319-34-5 Y
ATC code	N05CF03
PubChem	CID 5719
DrugBank	DB00962
ChemSpider	5517 Y
UNII	S62U433RMH Y
KEGG	D00530 Y
ChEBI	CHEBI:10102 Y
ChEMBL	CHEMBL1521 Y
Chemical data
Formula	C17H15N5O
Mol. mass	305.34
SMILES	eMolecules & PubChem
InChI InChI=1S/C17H15N5O/c1-3-21(12(2)23)15-6-4-5-13(9-15)16-7-8-19-17-14(10-18)11-20-22(16)17/h4-9,11H,3H2,1-2H3 Y Key:HUNXMJYCHXQEGX-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Zaleplon (marketed under the brand names Sonata and Starnoc) is a sedative/hypnotic, mainly used for insomnia. It is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class.^[1] In terms of adverse effects zaleplon appears to offer little improvement compared to both benzodiazepines and other non-benzodiazepine Z-drugs.^[2][3]

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.

Mechanism [link]

Zaleplon and Zolpidem both are agonists at the GABA A ɣ 1 subunit. It is also available as a white capsule tablet with no identifying markings. It is also prescribed for anxiety.

Clinical uses [link]

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.^[4]

Zaleplon is also effective in the treatment of middle of the night insomnia without causing residual hangover effects.^[5][6]

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.^[7]

Side-effects [link]

The side effects of zaleplon are similar to the side effects of benzodiazepines, although with less next-day sedation,^[2] 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.^[8][9]

Zaleplon may cause day-time drowsiness, dizziness, headache.

Available data cannot provide a reliable estimate of the incidence of dependence during treatment at recommended doses of Zaleplon. Other sedative/hypnotics have been associated with various signs and symptoms following abrupt discontinuation, ranging from mile dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. See Sonata (R) (zaleplon) Capsules, U.S. Physician Prescribing Information, available at https://www.pfizer.com/products/rx/rx_product_sonata.jsp (last visited Mar. 30, 2012). 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.^[10]

Some evidence suggests that Zaleplon tolerance and rebound effects may be less frequent than with other nonbenzodiazepine Z-drugs in its class.^[11]

Special precautions [link]

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.^[12]

Elderly [link]

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 nonbenzodiazepine (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.^[3]

Pharmacology [link]

Zaleplon selectively binds with high efficacy to the benzodiazepine site (ω₁) on the α₁ containing GABA_A receptors which produces its therapeutic hypnotic 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.^[13][14] Unlike non-selective benzodiazepine drugs and zopiclone which distort the sleep pattern zaleplon appears to induce sleep without disrupting the natural sleep architecture.^[15]

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.^[16]

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 GABA_A 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.^[17][18]

Chemistry [link]

Pure zaleplon in its solid state is a white to off-white powder that has very low solubility 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.

Pharmacokinetics [link]

Zaleplon is primarily metabolised by aldehyde oxidase, 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 [link]

Cimetidine, rifampicin and thioridazine cause interactions with zaleplon.^[19]

Recreational use [link]

Zaleplon (Sonata) has a relatively high potential to be abused. Often this use involves a different delivery method (insufflating) to induce effects faster.^[20]

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.^[21][22]

See also [link]

• Nonbenzodiazepine
• Z-drugs (excluding Zaleplon (Sonata))

• Zolpidem (Ambien)
• Zopiclone (Imovane)
• Eszopiclone (Lunesta)

References [link]