Peripheral benzodiazepine receptors, effect

Alpidem. Alpidem is an imidazopyridine partial agonist that also shows relative selectivity for the type I benzodiazepine receptor. Studies have shown an anxiolytic effect comparable with the classic benzodiazepines, but with an improved adverse effect profile [Pancheri et al. 1993). It has also been compared with buspirone in patients with generalized anxiety disorder and shown to be more rapidly effective and again to have a more favorable adverse effect profile [Legris et al. 1993). Longer-term studies with alpidem have shown that tolerance does not occur, and no significant problems of withdrawal on discontinuation were found [Chevalier et al. 1993). Alpidem was licensed in France for the treatment of anxiety but has now been suspended because of recent reports of alpidem-induced hepatic dysfunction. The reason for this is unclear, but it may be a reflection of the fact that alpidem also binds to peripheral benzodiazepine receptors, which are present in high density in the liver. 

Componnds of type 132, 133, 135, 137 and their derivatives showed ability to bind the central and peripheral benzodiazepine receptors [43,45,48,51,56], thereby promoting restoration of the damaged nerve endings. Effects of anti-inflammatory activity [9,25,61-64] of derivatives of 4-oxo-pyridazino[4,5-b]indole and 3-oxo-piridazino[4,3-b]indole were also reported. 

Biegon, A., Alvarado, M., Budinger, T.F., Grossman, R., Hensley, K., West, M.S., Kotake, Y., Ono, M., and Floyd, R.A. (2002). Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain. J. Neurochem. 82, 924-934. 

Nephentin is also a large polypeptide that has been shown to have a relatively high affinity for the benzodiazepine receptor and does not have any effect upon other neurotransmitter receptors. Unlike DBI, however, the concentration of nephentin is much higher in non-nervous peripheral tissues such as the bile duct than it is in the brain. Furthermore, the distribution of nephentin in the brain does not coincide with that of the benzodiazepine receptors. It is possible, nevertheless, that nephentin is a precursor of a lower molecular weight peptide that can block the benzodiazepine receptor. 

Desjardins P, Butterworth RE. The peripheral-type benzodiazepine ( 3) receptor in hyperam-monemic disorders. Neurochem. Int., 41, 109-114, 2002 Desjardins P, Bandeira P, Raghavendra Rao VL, Ledoux S, Butterworth RF. Increased expression of the peripheral-type benzodiazepine receptor-isoquinohne carboxamide binding protein in mRNA brain following portacaval anastomosis. Brain Res., 758, 255-258, 1997 Desjardins P, Rama Rao VK, Michalak A, Rose C, Butterworth RF. Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab. Brain Dis., 14, 273-282, 1999... 

Prettier E, Amri H, Li W, Brown R, Lin CS, Makariou E, Defeudis FV, Drieu K, Papadopoulos V (2006) Cancer-related overexpressirai of the peripheral-type benzodiazepine receptor and cytostatic anticancer effects of Ginkgo biloba extract (EGb 761). Anticancer Res 26(1 A) 9-22... 

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