Benzodiazepine-receptor agonist

The binding of [ H]Ro5-4864 to the benzodiazepine receptors of isolated guinea-pig alveolar type II cells indicated one population of binding sites with high affinity Kp = 5,7 nM) and saturability (B = 4.582 fM/mg membrane protein) (Das et al. 1987). 

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A medication that causes induction of sleep. The majority of currently available hypnotics (for example benzodiazepine receptor agonists) act via potentiating the brain s inhibitory GABAergic systems, in turn reducing the activity of arousal (i.e. wake promoting) neurotransmitter systems. 

THE BENZODIAZEPINE RECEPTOR AGONIST/INVERSE AGONIST SPECTRUM... 

Inadequate activity of an endogenous ligand which is a benzodiazepine receptor agonist and suppresses anxiety. In this case, the administration of the antagonist, fiumazenil, should induce anxiety in normal subjects and exacerbate anxiety in anxious patients. 

Benzodiazepine receptor agonists, including traditional benzodiazepines, zolpidem, zaleplon, and eszopiclone, are approved... 

FIGURE 38-1. Primary assessment and initial treatment for complaint of excessive daytime sleepiness. RLS, restless-legs syndrome NPSG, nocturnal polysomnography OSA, obstructive sleep apnea DA, dopamine agonist MSLT, multiple sleep latency test BZDRA, benzodiazepine receptor agonist SNRI, serotonin and norepinephrine reuptake inhibitor TCA, tricyclic antidepressant CPAP, continuous positive airway pressure. 

BZDRA benzodiazepine receptor agonist Reference lists and self-assessment questions and answers are... 

Altered ammonia, glutamate, benzodiazepine receptor agonists, and manganese are associated with HE. However, serum ammonia levels are poorly correlated with mental status in HE. 

FIGURE 72-1. Algorithm for treatment of dyssomnias. (BZDRA, benzodiazepine receptor agonist CPAP, continuous positive airway pressure.) (Adapted and reprinted with permission from Jermain DM, Sleep disorders. IntJann M, ed. Pharmacotherapy Self-Assessment Program, 2nd ed. Kansas City, MO, American College of Clinical Pharmacy, 1995 139-154.)... 

In addition to the benzodiazepine receptor agonists which, depending on the dose administered, have anxiolytic, anticonvulsant, sedative and amnestic properties, benzodiazepines have also been developed which block the action of agonists on this receptor. Such antagonists may be exemplified by... 

Zopiclone is widely used as a sedative-hypnotic. It is metabolized to an inactive N-desmethylated derivative and an active N-oxide compound, both of which contain chiral centres. S-Zopiclone has a 50-fold higher affinity for the benzodiazepine receptor site than the R-enantiomer. This could be therapeutically important, particularly if the formation and the urinary excretion of the active metabolite benefits the S-isomer, which appears to be the case. As the half-life of the R-enantiomer is longer than that of the S-form, it would seem advantageous to use the R-isomer in order to avoid the possibility of daytime sedation and hangover effects which commonly occur with long-acting benzodiazepine receptor agonists. 

Flumazenil Romazicon) is a benzodiazepine antagonist that specifically reverses the respiratory depression and hypnosis produced by the benzodiazepine receptor agonists. Its block of the amnesic effect of the agonists is less reliable. Flumazenil is particularly useful when an overdose of benzodiazepines has occurred. It is also employed when a benzodiazepine has been used to produce conscious sedation and rapid recovery of psychomotor competency is desirable. To avoid resedation, flumazenil may require administration by intravenous infusion. 

As indicated earlier, benzodiazepine receptor agonists selectively and specifically antagonized CCK-8S-induced excitation of rat hippocampal neurons. It... 

Mitler MM. Nonselective and selective benzodiazepine receptor agonists-where are we today Sleep 2000 23(suppl 1) S39-S47. 

The focus of this section will be the prevention of sleep loss through the use of sleep-promoting medications. Choice of sleep medications will not be considered, as others have thoroughly discussed this issue (6). Short-acting benzodiazepine receptor agonists are generally the type of medication recommended for the treatment of transient insomnia and chronic primary insomnia, and as adjunctive therapy for secondary chronic insomnias. 

As alcohol has pronounced sedative properties, it is not surprising to find that it facilitates central inhibitory transmission. It has been shown that alcohol has a direct effect on a portion of the GABA-benzodiazepine complex that controls the chloride ion channel. In clinical studies it has been shown that such inhibitory effects may be reversed by some partial inverse benzodiazepine receptor agonists, but their development as therapeutic agents has been discontinued because they do not reverse other detrimental effects of alcohol on brain function (see Figure 15.1). 

Alprazolam, 269, a popular sedative/hypnotic agent and benzodiazepine receptor agonist, has been labelled257 with 11C in metabolically stable position in reaction of the amidrazone, 7-chloro-5-phenyl-3//-l,4-benzodiazepine-2-yl hydrazone, 270, with 1-[ Cjacetyl chloride followed by pyrolysis of the resulting 1-acetylhydrazone 271. Compound 269 has been obtained in 43-65% yield during 40-55 min at specific activity 0.93-2.18 Ci /miol-1, and used for metabolism and tissue distribution studies257 (equation 107). 

In a double-blind, placebo-controlled study of sex differences in the effects of lorazepam in trained social drinkers, lorazepam substituted for alcohol equally in both sexes and increased associated scores for light-headedness (14). The women had much greater performance impairment in a digital symbol substitution test after lorazepam than the men. These results suggest that the stimulus and cognitive effects of benzodiazepine receptor agonists are modulated by different brain mechanisms. 

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