Sleep-inducing agents

Meparfyiiol, a mild hypnotic or sleep-inducing agent... 

Anxiolytics for the treatment of states of anxiety and tension of varied origins they are also called minor tranquillizers. The sleep-inducing agents (hypnotics) most used today are chemically and pharmacologically closely related to tranquillizers. 

The synthesis of yet another example begins with the allylation of the enamide (21-2) with methyl iodide. Reaction of this intermediate (23-1) as above with the ami-nopyrrazole (23-2) leads to the formation of the fused pyrimidinopyrrazole (23-3). This last productis is next acylated with thiazole-carboxillic acid (23-4) in the presence of aluminum chloride. There is thus obtained the sleep inducing agent indiplon (23-5) [24]. 

Neurotransmitters and NREM Sleep in Humans. Several agents that influence the brain levels of neurotransmitters have a profound effect on NREM sleep in humans. Most studies indicate that tryptophan, a precursor of serotonin, increases NREM sleep time and decreases sleep latency (38, 39). Tryptophan was used one time as a sleep-inducing agent, but it is no longer available because it causes eosinophilic myalgia syndrome. 

Barbiturates and benzodiazepines enhance the actions of the inhibitory neurotransmitter, gamma-aminobutyric acid (Fig 3.6). Tables 3.8A, 3.8B and 3.8C compare barbiturates and benzodiazepines. Agents from both classes are effective sedative-hypnotics (sleep-inducing agents), antianxiety agents, and anticonvulsants (Table 3.9). Physicians prescribe benzodiazepines more often than barbiturates because they cause fewer side effects. 

Valerian is a mild sedative and sleep-inducing agent that has an effect similar to benzodiazepines. It has been called herbal valium. However, Valerian has an odor of dirty socks making it a very low risk for overdose. There have been no reports that frequent use of Valerian leads to habituation and addiction. 

Compounds such as these play roles in the transmission of nerve impulses and exhibit other biological effects. For example, a lipid containing the amide analog of oleic acid [(Z)-9-octadecenamide] was recently identified as an essential sleep-inducing agent in the brain indeed, persons with hpid-restricted diets have difQculty experiencing deep sleep. 

Figure 7.33 Top an example of metabolic reduction of a ketone is seen for the narcotic antagonist naloxone. Bottom chloral hydrate (the active ingredient in a "Mickey Finn") exists in equilibrium with trichloroacetaldehyde. Some of this is oxidized to trichloroacetic acid which is not active as a hypnotic agent. The remainder gets metabolically reduced to 1,1,1-trichloroethanol, which is the active sleep-inducing agent.

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