Zaleplon nervous system

Both zolpidem and zaleplon appear to be nonfatal in overdose. However, overdoses in combination with other central nervous system (CNS) depressant agents pose a greater risk. Recommended treatment consists of general symptomatic and supportive measures, including gastric lavage. Use of flumazenil may be helpful. 

The benzodiazepines, the barbiturates, zolpidem, zaleplon, eszopiclone, and many other drugs bind to molecular components of the GABAa receptor in neuronal membranes in the central nervous system. This receptor, which functions... 

Tolerance—decreased responsiveness to a drug following repeated exposure—is a common feature of sedative-hypnotic use. It may result in the need for an increase in the dose required to maintain symptomatic improvement or to promote sleep. It is important to recognize that partial cross-tolerance occurs between the sedative-hypnotics described here and also with ethanol (see Chapter 23)—a feature of some clinical importance, as explained below. The mechanisms responsible for tolerance to sedative-hypnotics are not well understood. An increase in the rate of drug metabolism (metabolic tolerance) may be partly responsible in the case of chronic administration of barbiturates, but changes in responsiveness of the central nervous system (pharmacodynamic tolerance) are of greater importance for most sedative-hypnotics. In the case of benzodiazepines, the development of tolerance in animals has been associated with down-regulation of brain benzodiazepine receptors. Tolerance has been reported to occur with the extended use of zolpidem. Minimal tolerance was observed with the use of zaleplon over a 5-week period and eszopiclone over a 6-month period. 

Zaleplon has a pharmacological profile similar to benzodiazepines. Zaleplon is a full agonist for the benzodiazepine oq receptor located on the GABAa receptor ionophore complex in the brain, with lower affinity for the a2 and a3 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 [33-36]. 

Zaleplon and zolpidem have been compared in two concurrent multicenter, randomized, double-blind, placebo-controlled crossover studies in chronic insomniacs (12). In study 1, zaleplon 10 mg, zolpidem 10 mg, or placebo were given double-bhnd to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study (13). The subjects were gently awakened and given the medication at predetermined times, 5, 4, 3, or 2 hours before morning awakening, which occurred 8 hours after bedtime. When they awoke in the morning, subjective and objective assessments of residual effects of hypnotics were administered. There were no serious adverse experiences during the study all adverse events were mild to moderate. The most commonly reported adverse events associated with zaleplon were weakness and somnolence. Weakness, depersonalization, dizziness, and somnolence were the most frequent nervous system adverse events associated with zolpidem. 

NERVOUS SYSTEM DRUGS ANXIOLYTICS AND HYPNOTICS Zaleplon, zolpidem, zopidone... 

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