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Chemical Compound Review

Benzodiazepine     5,6- diazabicyclo[5.4.0]undeca- 2,4,7,9,11...

Synonyms: benzodiazepin, SureCN8137, AG-D-57976, SureCN11406717, LS-33991, ...
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Disease relevance of Benzodiazepine


Psychiatry related information on Benzodiazepine


High impact information on Benzodiazepine

  • We studied the effect of age on the pharmacokinetics and pharmacodynamics of the benzodiazepine hypnotic agent triazolam, now the most frequently prescribed hypnotic drug in the United States. METHODS [11].
  • There is a dramatic increase in the FSE2 binding complex when Fos levels are induced with serum, benzodiazepine, and nerve growth factor or are expressed from a v-fos gene [12].
  • GABA(A) (gamma-aminobutyric acid(A)) receptors are molecular substrates for the regulation of vigilance, anxiety, muscle tension, epileptogenic activity and memory functions, which is evident from the spectrum of actions elicited by clinically effective drugs acting at their modulatory benzodiazepine-binding site [13].
  • Thus, benzodiazepine-induced behavioural responses are mediated by specific GABA(A) receptor subtypes in distinct neuronal circuits, which is of interest for drug design [13].
  • Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor [14].

Chemical compound and disease context of Benzodiazepine


Biological context of Benzodiazepine

  • They reported that this substance is extremely potent in displacing 3H-diazepam from brain binding sites and proposed that a beta-carboline-3-carboxylic acid derivative might, in part, be the endogenous ligand for the brain benzodiazepine receptor [20].
  • Benzodiazepine and beta-adrenergic receptor ligands independently stimulate phospholipid methylation [21].
  • Amino-acid sequences derived from complementary DNAs encoding the alpha- and beta-subunits of the GABA/benzodiazepine receptor from bovine brain show homology with other ligand-gated receptor subunits, suggesting that there is a super-family of ion-channel-containing receptors [22].
  • Replacement of the two aliphatic residues with a benzodiazepine-based mimic of a peptide turn generated potent inhibitors of farnesyltransferase [50 percent inhibitory concentration (IC50) < 1 nM] [23].
  • These results suggest that purines may represent endogenous substances that regulate food intake through interactions with the benzodiazepine receptor [24].

Anatomical context of Benzodiazepine


Associations of Benzodiazepine with other chemical compounds


Gene context of Benzodiazepine

  • Benzodiazepine anxiolytic drugs also increase serum GH levels in man, by a mechanism that has not been clearly established [36].
  • CONCLUSIONS: In cognitively intact, older adults, the effect of the APOE epsilon4 allele is not necessarily seen in the immediate response to benzodiazepine challenge [37].
  • The peripheral benzodiazepine receptor (pBR) ligand, PK11195, promotes mitochondrial apoptosis and blocks P-glycoprotein (Pgp)-mediated drug efflux to chemosensitize cancer cells at least as well or better than the Pgp modulator, cyclosporine A (CSA) [38].
  • The mammalian GABAA/benzodiazepine (GABAA/BZ) receptor is comprised of several subunit isoforms: alpha 1-6, beta 1-13, gamma 1-3 and delta [39].
  • Deletion of the gamma2 subunit in the third postnatal week resulted in loss of benzodiazepine-binding sites and parallel loss of punctate immunoreactivity for postsynaptic GABA(A) receptors and gephyrin [40].

Analytical, diagnostic and therapeutic context of Benzodiazepine


  1. Benzodiazepine compounds and hepatic encephalopathy. Mullen, K.D. N. Engl. J. Med. (1991) [Pubmed]
  2. Elevated brain concentrations of 1,4-benzodiazepines in fulminant hepatic failure. Basile, A.S., Hughes, R.D., Harrison, P.M., Murata, Y., Pannell, L., Jones, E.A., Williams, R., Skolnick, P. N. Engl. J. Med. (1991) [Pubmed]
  3. Mammalian peripheral-type benzodiazepine receptor is homologous to CrtK protein of rhodobacter capsulatus, a photosynthetic bacterium. Baker, M.E., Fanestil, D.D. Cell (1991) [Pubmed]
  4. The effects of benzodiazepine-receptor antagonists and partial inverse agonists on acute hepatic encephalopathy in the rat. Bosman, D.K., van den Buijs, C.A., de Haan, J.G., Maas, M.A., Chamuleau, R.A. Gastroenterology (1991) [Pubmed]
  5. Effects of the benzodiazepine receptor antagonist flumazenil in hepatic encephalopathy in humans. Bansky, G., Meier, P.J., Riederer, E., Walser, H., Ziegler, W.H., Schmid, M. Gastroenterology (1989) [Pubmed]
  6. A benzodiazepine used in the treatment of insomnia phase-shifts the mammalian circadian clock. Turek, F.W., Losee-Olson, S. Nature (1986) [Pubmed]
  7. Molecular and neuronal substrate for the selective attenuation of anxiety. Löw, K., Crestani, F., Keist, R., Benke, D., Brünig, I., Benson, J.A., Fritschy, J.M., Rülicke, T., Bluethmann, H., Möhler, H., Rudolph, U. Science (2000) [Pubmed]
  8. Rebound insomnia: a new clinical syndrome. Kales, A., Scharf, M.B., Kales, J.D. Science (1978) [Pubmed]
  9. NMDA receptor losses in putamen from patients with Huntington's disease. Young, A.B., Greenamyre, J.T., Hollingsworth, Z., Albin, R., D'Amato, C., Shoulson, I., Penney, J.B. Science (1988) [Pubmed]
  10. Early morning insomnia with rapidly eliminated benzodiazepines. Kales, A., Soldatos, C.R., Bixler, E.O., Kales, J.D. Science (1983) [Pubmed]
  11. Sensitivity to triazolam in the elderly. Greenblatt, D.J., Harmatz, J.S., Shapiro, L., Engelhardt, N., Gouthro, T.A., Shader, R.I. N. Engl. J. Med. (1991) [Pubmed]
  12. Common DNA binding site for Fos protein complexes and transcription factor AP-1. Rauscher, F.J., Sambucetti, L.C., Curran, T., Distel, R.J., Spiegelman, B.M. Cell (1988) [Pubmed]
  13. Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor subtypes. Rudolph, U., Crestani, F., Benke, D., Brünig, I., Benson, J.A., Fritschy, J.M., Martin, J.R., Bluethmann, H., Möhler, H. Nature (1999) [Pubmed]
  14. Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Korpi, E.R., Kleingoor, C., Kettenmann, H., Seeburg, P.H. Nature (1993) [Pubmed]
  15. Ligands specific to peripheral benzodiazepine receptors for treatment of porphyrias. Katz, Y., Weizman, A., Gavish, M. Lancet (1989) [Pubmed]
  16. Identification by positron emission tomography of neuronal loss in acute vegetative state. Rudolf, J., Sobesky, J., Grond, M., Heiss, W.D. Lancet (2000) [Pubmed]
  17. Hepatic encephalopathy in rats with thioacetamide-induced acute liver failure is not mediated by endogenous benzodiazepines. Püspök, A., Herneth, A., Steindl, P., Ferenci, P. Gastroenterology (1993) [Pubmed]
  18. Efficacy of dexamethasone in benzodiazepine-resistant delirium tremens. Fischer, D.K., Simpson, R.K., Smith, F.A., Mattox, K.L. Lancet (1988) [Pubmed]
  19. Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy. Nemni, R., Braghi, S., Natali-Sora, M.G., Lampasona, V., Bonifacio, E., Comi, G., Canal, N. Ann. Neurol. (1994) [Pubmed]
  20. beta-Carboline-3-carboxylic acid ethyl ester antagonizes diazepam activity. Tenen, S.S., Hirsch, J.D. Nature (1980) [Pubmed]
  21. Benzodiazepine and beta-adrenergic receptor ligands independently stimulate phospholipid methylation. Strittmatter, W.J., Hirata, F., Axelrod, J., Mallorga, P., Tallman, J.F., Henneberry, R.C. Nature (1979) [Pubmed]
  22. Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family. Schofield, P.R., Darlison, M.G., Fujita, N., Burt, D.R., Stephenson, F.A., Rodriguez, H., Rhee, L.M., Ramachandran, J., Reale, V., Glencorse, T.A. Nature (1987) [Pubmed]
  23. Benzodiazepine peptidomimetics: potent inhibitors of Ras farnesylation in animal cells. James, G.L., Goldstein, J.L., Brown, M.S., Rawson, T.E., Somers, T.C., McDowell, R.S., Crowley, C.W., Lucas, B.K., Levinson, A.D., Marsters, J.C. Science (1993) [Pubmed]
  24. Purinergic regulation of food intake. Levine, A.S., Morley, J.E. Science (1982) [Pubmed]
  25. Chronic benzodiazepine treatment decreases postsynaptic GABA sensitivity. Gallager, D.W., Lakoski, J.M., Gonsalves, S.F., Rauch, S.L. Nature (1984) [Pubmed]
  26. Ethyl beta-carboline-3-carboxylate shows differential benzodiazepine receptor interaction. Nielsen, M., Braestrup, C. Nature (1980) [Pubmed]
  27. Cerebellar GABAA receptor selective for a behavioural alcohol antagonist. Lüddens, H., Pritchett, D.B., Köhler, M., Killisch, I., Keinänen, K., Monyer, H., Sprengel, R., Seeburg, P.H. Nature (1990) [Pubmed]
  28. Differential localization of type I and type II benzodiazepine binding sites in substantia nigra. Lo, M.M., Niehoff, D.L., Kuhar, M.J., Snyder, S.H. Nature (1983) [Pubmed]
  29. A selective imidazobenzodiazepine antagonist of ethanol in the rat. Suzdak, P.D., Glowa, J.R., Crawley, J.N., Schwartz, R.D., Skolnick, P., Paul, S.M. Science (1986) [Pubmed]
  30. Pentobarbital: dual actions to increase brain benzodiazepine receptor affinity. Skolnick, P., Moncada, V., Barker, J.L., Paul, S.M. Science (1981) [Pubmed]
  31. Neurotransmitter receptor binding in bovine cerebral microvessels. Peroutka, S.J., Moskowitz, M.A., Reinhard, J.F., Snyder, S.H. Science (1980) [Pubmed]
  32. Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Feely, M., Calvert, R., Gibson, J. Lancet (1982) [Pubmed]
  33. A benzodiazepine receptor-mediated model of anxiety. Studies in nonhuman primates and clinical implications. Insel, T.R., Ninan, P.T., Aloi, J., Jimerson, D.C., Skolnick, P., Paul, S.M. Arch. Gen. Psychiatry (1984) [Pubmed]
  34. Insertion of alpha7 nicotinic receptors at neocortical layer V GABAergic synapses is induced by a benzodiazepine, midazolam. Yamamoto, S., Yamada, J., Ueno, S., Kubota, H., Furukawa, T., Yamamoto, S., Fukuda, A. Cereb. Cortex (2007) [Pubmed]
  35. Proximity-accelerated chemical coupling reaction in the benzodiazepine-binding site of gamma-aminobutyric acid type A receptors: superposition of different allosteric modulators. Tan, K.R., Gonthier, A., Baur, R., Ernst, M., Goeldner, M., Sigel, E. J. Biol. Chem. (2007) [Pubmed]
  36. The effect of buspirone on prolactin and growth hormone secretion in man. Meltzer, H.Y., Flemming, R., Robertson, A. Arch. Gen. Psychiatry (1983) [Pubmed]
  37. Apolipoprotein E epsilon4 allele and lorazepam effects on memory in high-functioning older adults. Pomara, N., Willoughby, L., Wesnes, K., Greenblatt, D.J., Sidtis, J.J. Arch. Gen. Psychiatry (2005) [Pubmed]
  38. PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism. Walter, R.B., Pirga, J.L., Cronk, M.R., Mayer, S., Appelbaum, F.R., Banker, D.E. Blood (2005) [Pubmed]
  39. Uncoupling of GABAA/benzodiazepine receptor alpha 1, beta 2, and gamma 2 subunit mRNA expression in cerebellar Purkinje cells of staggerer mutant mice. Luntz-Leybman, V., Rotter, A., Zdilar, D., Frostholm, A. J. Neurosci. (1995) [Pubmed]
  40. The gamma 2 subunit of GABA(A) receptors is required for maintenance of receptors at mature synapses. Schweizer, C., Balsiger, S., Bluethmann, H., Mansuy, I.M., Fritschy, J.M., Mohler, H., Lüscher, B. Mol. Cell. Neurosci. (2003) [Pubmed]
  41. Cerebral uptake of benzodiazepine measured by positron emission tomography in hepatic encephalopathy. Samson, Y., Bernuau, J., Pappata, S., Chavoix, C., Baron, J.C., Maziere, M.A. N. Engl. J. Med. (1987) [Pubmed]
  42. Withdrawal reaction after long-term therapeutic use of benzodiazepines. Busto, U., Sellers, E.M., Naranjo, C.A., Cappell, H., Sanchez-Craig, M., Sykora, K. N. Engl. J. Med. (1986) [Pubmed]
  43. Precipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15-1788) after 7 days of diazepam. Lukas, S.E., Griffiths, R.R. Science (1982) [Pubmed]
  44. The poisoned patient with altered consciousness. Controversies in the use of a 'coma cocktail'. Hoffman, R.S., Goldfrank, L.R. JAMA (1995) [Pubmed]
  45. Consequences of the 1989 New York State triplicate benzodiazepine prescription regulations. Weintraub, M., Singh, S., Byrne, L., Maharaj, K., Guttmacher, L. JAMA (1991) [Pubmed]
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