Zaleplon 151319-34-5

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 5 weeks without the risk of dependence or rebound insomnia 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 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,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 or drug dependence may occur. Stopping this medication suddenly after prolonged or frequent use may cause withdrawal effects such as mood changes, anxiety, restlessness or rebound insomnia. 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 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 , 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. 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 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.