Biological sedative effect

The initial observation was based on the fact that the triazolopyridazine CL 218,872 had a significantly higher affinity for receptors in the cerebellum (benzodiazepine type 1 receptor) than it had for receptors in the hippocampus (benzodiazepine type 11 receptor) (Klepner et al. 1979). CL 218,872 was also known to be an anxiolytic without sedative effects. The proposal was that anxiolysis was mediated by the receptors in the cerebellum, whereas sedation was mediated by receptors elsewhere. Subsequent work has shown that the case is not as simple as that. With the advent of molecular biology and coexpression studies, it has been established that the oc,p2y2 receptor is equivalent to the type 1 receptor. The type 11 receptors appear to be a more heterogeneous receptor class as 3p2y2/ P2y2 seem to display... 

For example, it is not uncommon when working in a mental health inpatient unit to see medication administered to reduce or eliminate violent or self-destructive behavior. The medication s sedative effect will calm one person immediately and may produce sleep another client of similar age, weight, and height may remain extremely combative. In order to achieve the same result, the second client may require a subsequent dose. Why does this happen There are no definitive or easy explanations for variability in client responses to medications. In many cases the combination of the client s unique biological system coupled with the variability of medications confirms that the use and application of medication is not an exact science. 

Using molecular biological techniques, point mutations of the a subunits have revealed that the sedative effects of the benzodiazepines likely result from an Interaction with the ai subunit, whereas the anxiolytic effects result from an interaction at the 02 subunit (27,28), as shown in Figure 15.10 and Table 15.3. Nonbenzodiazepine receptor agonists, such as the sedative-hypnotics indiplon, zaleplon, zolpicone, and zolpidem (see Chapter 19), are ai subunit-preferring ligands, as shown in Table 15.3 (29). 

Documented effects The biological activity is due to the presence of saponins, and removal of the saponins from the tincture leads to complete loss of the pharmacological properties (Ivanova 1963). The sedative effect of this species is nearly twice as strong as that of Valeriana (Tolmachev 1976). The roots of this species reduce excitability of the nervous system. Clinical tests showed that application of an alcohol infusion stopped or noticeably reduced chest pain as well as nervous and cardiovascular excitation caused by hypodermic introduction of caffeine (Akopov 1990). 

The following biological effects are mentioned in patents for 4-oxo-4M-pyrido[l,2-a]pyrimidines CNS activity, including antipyretic, tranquilizer, sedative, analgesic and/or muscle relaxant effects,55,56,59,66,72,74,... 

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