Zaleplon

Drugbox
IUPAC_name = "N"-(3-(3-cyanopyrazolo [1,5-"a"] pyrimidin-7-yl)phenyl)-"N"- ethylacetamide

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width=140
CAS_number= 151319-34-5
ATC_prefix=N05
ATC_suffix=CF03
ATC_supplemental=
PubChem=5719
DrugBank=APRD00411
C=17 | H=15 | N=5 | O=1
molecular_weight = 305.34
bioavailability= 30% (oral)
metabolism = Hepatic
elimination_half-life= 1 hour
excretion = Renal
pregnancy_US = C
legal_US = Schedule IV
routes_of_administration= Oral

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. Sonata (US) is manufactured by King Pharm. of Bristol, TN; Starnoc has been discontinued in Canada.

Chemistry

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.

Clinical uses

Zaleplon is efficacious 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 5 weeks without the risk of dependence or rebound insomnia upon discontinuation. [cite journal | journal =Sleep Med | year =2000 |month=Feb | pages =41-49 | title =A five week, polysomnographic assessment of zaleplon 10 mg for the treatment of primary insomnia | author =Walsh JK | coauthors =Vogel GW, Scharf M, Erman M, William Erwin C , Schweitzer PK, Mangano RM, Roth T | pmid =10733619 ]

Pharmacology

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.

Zaleplon interacts with the GABA receptor complex and shares some of the pharmacological properties of the benzodiazepines. Although not a benzodiazepine, zaleplon can cause similar effects: anterograde amnesia (forgetting the period during the effects) as the most common.

Zaleplon is primarily metabolised by aldehyde oxidase, and its half-life can be affected by substances which inhibit or induce aldehyde oxidase.

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. [cite journal | last = Dündar | first = Y | coauthors = Dodd S, Strobl J, Boland A, Dickson R, Walley T. | year = 2004 | month = Jul | title = Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis | journal = Hum Psychopharmacol. | volume = 19 | issue = 5 | pages = 305–22 | pmid = 15252823 | doi = 10.1002/hup.594 ]

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 by its binding to the central nervous system (CNS) type benzodiazepine receptors. The elimination half life of zaleplon is 1 hour irrespective of dose. 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 zaelplon 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. [cite journal | author = Noguchi H | coauthors = Kitazumi K, Mori M, Shiba T. | year = 2004 | month = Mar | title = Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats | journal = J Pharmacol Sci. | volume = 94 | issue = 3 | pages = 246–51 | pmid = 15037809 | url = http://www.jstage.jst.go.jp/article/jphs/94/3/246/_pdf | format = pdf | doi = 10.1254/jphs.94.246 ]

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 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. [cite journal | journal = Am J Geriatr Pharmacother | year = 2006 | month = Jun | volume = 4 | issue = 2 | pages = 168–92 | title = Management of chronic insomnia in elderly persons | author = Bain KT | pmid = 16860264 | doi = 10.1016/j.amjopharm.2006.06.006]

ide-effects

The side effects of zaleplon are similar to the side effects of benzodiazepines. [cite journal | journal =Ann Pharmacother | year =1998 | pages =680-91 | month =Jun | title =Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia | author =Wagner J | coauthors =Wagner ML, Hening WA | pmid =9640488 ]

Zaleplon may cause hallucinations, abnormal behavior, severe confusion, day-time drowsiness, dizziness or lightheadedness, unsteadiness and/or falls, double vision or other vision problems, agitation, headache, nausea, vomiting, diarrhea or abdominal pain, depression, muscle weakness, tremor, vivid or abnormal dreams and memory difficulties or amnesia.

Zaleplon is habit-forming, meaning addiction may occur. Stopping this medication suddenly after prolonged or frequent use may cause withdrawal effects such as mood changes, anxiety, and restlessness.

Recreational use

Zaleplon (Sonata) has a relatively high potential to be abused. Often this use involves a different delivery method (insufflation) to induce effects faster.

The side effects of zaleplon are greatly increased when taken improperly, especially anterograde amnesia - the inability to remember the time during which one was under the influence of the drug. Because of this, a person may lose track of how much zaleplon they ingested, and take more than they originally intended. Zaleplon is a nonbenzodiazepine drug, and research on other drugs in this class has indicated that their potential for abuse was far lower than that of benzodiazepine drugs, but that they still carried a risk higher than first believed. The study specifically mentions persons with prior substance abuse problems as individuals with a high risk for addiction to nonbenzodiazepine type drugs. [ [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14519173&dopt=Abstract Abuse and dependence potential for the non-benzodi... [Addiction. 2003 - PubMed Result ] ]

References