Standard hypnotics

Despite widespread use of standard hypnotics and sedating antidepressants for chronic insomnia, their role for this indication still needs to be defined by further research [8], In particular, clinicians must be cautious with antidepressants, which disturb sleep architecture and have various side effects [54, 55],... 

Many studies have tested tryptophan as a hypnotic agent. While the results have been variable, the consensus of reviews is that under certain conditions tryptophan can be an effective hypnotic.54-57 Although in severe insomnia tryptophan is not as effective as standard hypnotics, in mild insomnia it is able to decrease sleep latency by about one half. It can be useful at low doses (<4 g) without altering sleep architecture.58... 

Breen D, Karabinis A, Malbrain M, Morais R, Albrecht S, Jarnvig IL, Parkinson P, Kirkham AJ. Decreased duration of mechanical ventilation when comparing analgesia-based sedation using remifentanil with standard hypnotic-based sedation for up to 10 days in intensive care unit patients a randomised trial. Grit Care 2005 9(3) R200-10. 

This "hangover" seemed severe enoixgh to eliminate the 30 mg dose range for clinical use as a hypnotic. A comparison study of A -THC at doses aroiind 20 mg with a standard hypnotic is in progress. 

Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

NMR-assay of meclizine (I) and methaqualone (II), besides a number of other potent hypnotics and their corresponding mixtures have been successfully carried out using an external standardization procedure reported. It is, however, interesting to observe that additional sources of variability are usually incorporated into an assay employing external standardization, and the same has been duly shown in the results thus obtained i.e., a large coefficient of variation to the extent of 4% achieved. 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

Andrade et al. (169a) conducted a placebo-controlled, double-blind study, which found that a mean stable dose of 5.4 mg of melatonin was helpful for initial insomnia in medically-ill patients for whom standard sedative-hypnotics may be problematic. 

Methods of assessing rebound and withdrawal in more clinically relevant terms have been available for many years (e.g., [8]). In the past decade, regulatory authorities have insisted on discontinuation studies after short-term use as well as long-term maintenance or relapse prevention. This applies to hypnotics in equal force despite most product licences now restricting hypnotic use to short-term (2 1 weeks) use. An adequate number of subjects, normal and insomniac, must be studied. Rebound needs assessment over more than one night, with a variety of techniques including PSG, activity meters, and subjective reports. Standard sleep questionnaires can be used for the subjective assessments. 

Zopiclone was the first of the new sedative-hypnotics to be launched in the late 1970s and has been shown to be equi-effective with the standard sedative-hypnotic benzodiazepines such as flurazepam and temazepam. There is evidence that zopiclone may cause less "hang-over effects than the conventional benzodiazepines but some studies have shown that this drug does produce performance decrement when this is tested shortly after treatment. A similar profile has been reported for zolpidem while abercarnil... 

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. 

Table 13. Standard solutions of volatile hypnotic drugs...

A state is an altered state if it is discretely different from some baseline state we want to compare things to. Since we usually take ordinary waking consciousness as our standard of comparison, a state such as nocturnal dreaming is thus an altered state. Other well-known examples of altered states are the hypnotic state, states induced by psychoactive drugs such as alcohol, states centered on strong emotions such as rage, panic, depression, and elation, and states induced by meditative practices. ... 

Let US look at a modern hypnotic procedure, the administration of the Stanford Hypnotic Susceptibility Scale, Form C. This is a standardized psychological test procedure widely used in research for determining how hypnotizable a subject is. 

There is nothing obviously theatrical or mysterious about administering the scale. The hypnotist does not wear a cloak or gesture hypnotically, there is no Look into my eyes rigmarole. It is standardized to the point where, after initially getting acquainted, the procedure is read word for word from printed instructions. Responses are evaluated in a standardized way Does the subject s arm move less than x inches iny seconds , for example. 

This standardized induction procedure takes between twelve and fifteen minutes, depending on how rapidly the hypnotist reads the script. Following this induction, a standard set of instructions is followed to test how responsive the subject is, how deeply hypnotized he is. 

I have hypnotized people with these standardized tests and seen these phenomena dozens and dozens of times. I must accept their reality because of my repeated experience. Or must I. ... 

Derivatives of /V-alkylbenzophenones and peptidoamino-benzophenones undergo hydrolysis, with subsequent intramolecular condensation that results in the formation of the 1,4-benzodiazepine hypnotics. A number of such compounds, e.g. rilmazafone (140), were suggested to have more beneficial pharmacological properties in comparison to standard benzodiazepines. Rilmazafone is a ring-opened derivative of 1,4-benzodiazepine (Scheme 25) and was developed in Japan... 

Hj-Lorazepam, 3-hydroxy-1,4-benzodiazepine, 45, a sedative hypnotic and antianxiety agent, has been synthesized in a seven-step procedure presented in equation 12 for use as an internal standard in GC-MS-NICI-SIM (NICl-SIM = negative ion chemical ionization-selective ion monitoring) quantitative analysis of this drug in complex matrices encountered in forensic work and for study of its complex kinetics. The procedure involved selective trideuteriation, protection of the amino group and... 

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