Benzodiazepines actions

Rudolph U, Crestani F, Benke D et al (1999) Benzodiazepine actions mediated by specific y-aminobutyric acidA receptor subtypes. Nature 401 796-800... 

Baraldi M, Guidotti A, Schwartz JP, Costa E GABA receptors in clonal cell lines A model for study of benzodiazepine action at molecular level. Science 1979 205 821-823. 

Rudolph, U., Crestani, F., Benke, D., Brunig, I., Benson, J. A., Fritschy, J. M., et al. (1999) Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor sub-types. Nature 401, 796-800. 

GABA Flavonoids present in ginkgo may endow it with benzodiazepine actions but it remains in question whether they cross the blood-brain barrer (Lobstein-Guth et al. 1988 Baureithel et al. 

There have been no formal studies of the toxicity of passionflower, but adverse effects have not been reported. There is one report of a case of inflammatory vasculitis associated with a preparation of passionflower (Smith et al. 1993). Like other herbs in this category, its putative benzodiazepine action contraindicates its combined use with other CNS depressants. 

Riban V, Bouilleret V, Pham-L BT, Fritschy JM, Marescaux C, Depaulis A (2002) Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience 112 101-111 Rudolph U, Crestani F, Benke D, Brunig I, Benson J, Fritschy JM, Martin JR, Bluethmann H, Mohler H (1999) Benzodiazepine actions mediated by specific y-aminobutyric acid A receptor subtypes. Nature 401 796-800... 

The benzodiazepine derivatives class of antianxiety agents shares the property of binding to a benzodiazepine receptor, part of the GABA receptor-chloride channel complex whose function it modulates allosterically. Not only the anxiolytic effects of the benzodiazepines, but also the anticonvulsant, sedative, or muscle relaxant effects seem to be mediated by the GABA-related mechanism. Besides the direct involvement of the GABA system, in parallel or more downstream to this, several other neurotransmitters such as serotonin have been suggested to participate in different aspects of benzodiazepine action. 

Following GI absorption or IV administration, benzodk azepines are rapidly distributed to the CNS. Subsequently, benzodiazepines are more slowly redistributed from the CNS to more poorly perfused tissue, such as adipose tissue and muscle. The rate of this redistribution is an important determinant of the duration of action of benzodiazepines and, like that for GI absorption, is largely determined by drug lipophihcity, with the more lipophilic drugs, such as midazolam and triazolam, having the shortest duration of action. Additional factors that influence the duration of benzodiazepine action are hepatic metaboHsm and acute tolerance, resulting in decreased response to benzodiazepines with continued drug exposure. 

In a patient lacking liver function, benzodiazepines that are metabolized via extrahepatic conjugation (e.g., lorazepam, oxazepam) are safer in terms of the possibility of excessive CNS depression. Lorazepam is metabolized, probably in the lungs, via glucuronidation. Although benzodiazepine actions can be reversed, the drug that acts as an antagonist is flumazenil, not naloxone. 

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