Peripheral benzodiazepine

Awad, M and Gavish, M (1987) Binding of [ H]Ro 5-4864 and [ H]PK 11195 to cerebral cortex and peripheral tissues of various species species differences and heterogeneity in peripheral benzodiazepine binding sites. J. Neurochem. 49 1407-1414. 

Drugan, RC, Basile, AS, Crawley, JN, Paul, SM and Skolnick, P (1987) Peripheral benzodiazepine binding sites in the Maudsley Reactive rat selective decrease confined to peripheral tissues. Brain Res. Bull. 18 143-145. 

Norenberg MD, Itzhak Y, Bender S The peripheral benzodiazepine receptor and neurosteroids in hepatic encephalopathy. Adv Exp Med Biol 1997 420 95-111. 

Zanoli P, Giacobazzi A, Vaccari G, Zeneroli ML, Baraldi M Up-regulation of peripheral benzodiazepine receptors in brain areas of rats with galactosamine-induced hepatic encephalopathy in Bengtsson F, Jeppson B (eds) Progress in Hepatic Encephalopathy. Miami, CRC Press, 1991, pp 161-168. 

Several different changes in mitochondria occur during apoptosis. These include a change in membrane potential (usually depolarization), increased production of reactive oxygen species, potassium channel activation, calcium ion uptake, increased membrane permeability and release of cytochrome c and apoptosis inducing factor (AIF) [25]. Increased permeability of the mitochondrial membranes is a pivotal event in apoptosis and appears to result from the formation of pores in the membrane the proteins that form such permeability transition pores (PTP) may include a voltage-dependent anion channel (VDAC), the adenine nucleotide translocator, cyclophilin D, the peripheral benzodiazepine receptor, hexokinase and... 

Papadopouios V, Widmaier EP, Amri H, Ziiz A, Li H, Culty M, Castello R, Philip GH, Sridaran R, Drieu K. (1998). In vivo studies on the roie of the peripheral benzodiazepine receptor (PBR) in steroidogenesis. Endocr Res. 124(3-4) 479-87. 

Diazepinomicin (ECO-4601) (191) Dibenzo- diazepine alkaloid Diazepinomicin (ECO-4601) (191) Oncology RAS-mitogen-activated phosphokinase (MAPK) pathway inhibitor and inhibition of tiie peripheral benzodiazepine receptor Phase I/II Thallion (Ecopia) 906-910... 

Gourdeau H, McAlpine JB, Ranger M, Simard B, Berger F, Beaudry F, Falardeau P. (2008) Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand. Cancer Chemother Pharmacol 61 911-921. 

A recent study found that cortical peripheral benzodiazepine receptors, as assessed with PET and [ C]PK11195, were increased by 30-40% in patients with AD when compared with healthy controls. This suggests active inflammatory processes in AD since PK11195 binds to activated microglia [72]. Several F-labeled tracers of the peripheral benzodiazepine receptor have been developed, and [i8p]PK14105 [73] and [i8p]FEDAA1106 [74] are the most well characterized. However, no reports have been published on the use of either of the two radiotracers in AD. The molecular structures of F-labeled tracers for the peripheral benzodiazepine receptor are shown in Fig. 5. 

D. Diorio, S.A. Weiner, R.F. Butterworth, M.J. Meaney, B.E. Suranyi-Cadotte, Peripheral benzodiazepine binding sites in Alzheimer s disease frontal and temporal cortex, Neurobiol. Aging 12 (1991) 255-258. 

G.W. Price, R.G. Ahier, S.P. Hume, R. Myers, L. Manjil, J.E. Cremer, S.K. Luthra, C. Pascali, V. Pike, R.S.J. Frackowiak, In vivo binding to peripheral benzodiazepine binding sites in lesioned rat brain Comparison between [ H]PK11195 and f F] PK14105 as markers for neuronal damage, J. Neurochem. 55 (1990) 175-185. 

M.-R. Zhang, J. Maeda, M. Ogawa, J. Noguchi, T. Ito, Y. Yoshida, T. Okauchi, S. Obayashi, T. Suhara, K. Suzuki, Development of a new radioligand, A/-(5-fluoro-2-phenoxyphenyl)-A/-(2[ F]fluoroethyl-5-methoxybenzyl)acetamide, for PET imaging of peripheral benzodiazepine receptor in primate brain, J. Med. Chem. 47 (2004) 2228-2235. 

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. 

Drugan RC, Philip HV Central and peripheral benzodiazepine receptors involvement in an organism s response to physical and psychological stress. Neurosci BehavRev 15 277, 1991... 

Pyrrolo[3,4-, ]pyridine derivatives, 147, have been prepared for comparison to the activity of alpidem, an anxiolytic imidazopyridine <1996JME4275>. The reduced derivative shows a significant affinity for the central benzodiazepine receptor. In contrast, the a,/3-unsaturated derivative shows significant affinity for the peripheral benzodiazepine receptor. 

Cinone, N., Holtje, H.-D., Carotti, A. Development of a Unique 3D Interaction Model of Endogenous and Synthetic Peripheral Benzodiazepine Receptor Ligands. /. Comput.-Aided Mol. Des. 2000, 14, 753-768. 

The third type of benzodiazepine receptor is the so-called peripheral benzodiazepine receptor (pBz). This was first discovered in the rat adrenal gland, hence the term "peripheral". However, it is now known to occur on the platelet membrane, on immune cells and also in the mammalian brain. 

Figure 17.3. Permeability transition pore (PTP). The PTP consists of voltage-dependent anion channel (VDAC), adenine nucleotide translocase (ANT) and several associated molecules including cyclophilin D (CypD) and peripheral benzodiazepine receptor (PBR). IMM, inner mitochondrial membrane OMM, outer mitochondrial membrane CytC, cytochrome c.

It should be noted that in addition to the GABA(A)-R benzodiazepine-binding sites or central benzodiazepine Rs (CBZ-Rs) there are peripheral benzodiazepine Rs (PBZ-Rs) associated with the outer membrane of mitochondria in glial cells and cells of peripheral tissue and which are involved in cholesterol transport and hence in regulation of steroid hormone synthesis. The GABA(B)-Rs are metabotropic and coupled via heterotrimeric G proteins to Ca2+ and K+ channels (Chapter 5). The psychotropic GABA breakdown product y-hydroxybutyrate (GHB) also acts via heterodimeric G protein-linked receptors (see Chapter 5). 

PBZ-R, peripheral benzodiazepine receptor P-Ca2+ GH, P-type voltage-gated Ca2+ channel... 

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