[Recent progress in development of psychotropic drugs (5)--Hypnotics]

Regarding the treatment of insomnia, it is said that a considerable degree of advancement has been made to date in terms of controlling toxicity, preventing the development of tolerance and avoiding addiction, which were often observed when administering barbiturates. Nevertheless, the majority of hypnotics used today, which are benzodiazepines, still retain certain side effects such as hangover effects, development of dependence, rebound insomnia as a withdrawal symptom, muscular atonia resulting in falling down and causing bone fracture, inhibition of respiratory system, negative interaction with alcohol, etc. The current trend of selecting hypnotics is to use short-half-life agents. However, there are yet other problems such as cognitive disorders including amnesia, rebound insomnia and increased anxiety during the daytime. In order to cope with these problems, three new hypnotics have recently been developed. They are non-benzodiazepine derivatives and considered to be safer than the others, because they are supposed to cause less side effects than conventional hypnotics. The pharmacokinetic characteristics of these new hypnotics can be summarized as follows: 1) these hypnotics have selective affinity to benzodiazepine receptor omega-1 subtype although the agent itself does not belong to the benzodiazepine derivative family; 2) the half-life-time in the serum is extremely short, namely 1-2 hours; 3) they increase the level of slow waves (delta-wave) during sleep; 4) they have a lesser effect toward atonic muscle and amnestic thought and behavioral disturbance as compared to conventional hypnotics; and 5) the risks of developing drug tolerance and reciprocal negative effects with alcohol are smaller. Consequently, we can expect that these new hypnotics will bring a certain advantage, especially regarding the avoidance of hypnotics-induced side effects in the course of clinical treatment of insomnia in the future.