Diazepam receptor interactions

The disinhibitory effects of 5-HT3 receptor antagonists are now well documented [29, 30]. These compounds act to restore normal behaviour to animals in conditions which are mildly aversive, such as a novel brightly lit test area. Such effects may be predictive of anxiolytic activity. An example of such disinhibition is the effect of ondansetron in the rat social interaction test in which the level of interaction between two rats is measured under certain defined conditions [29]. In non-aversive conditions this type of behaviour is quite marked, but it is suppressed in novel highly illuminated conditions. Ondansetron overcomes this suppression, as do known anxiolytics such as diazepam. 

Wahlestedt C, Pich EM, Koob GF, et al Modulation of anxiety and neuropeptide Y-Yl receptors by antisense oligodeoxynucleotides. Science 259 528-531, 1993 Waka T, Fukada N Pharmacologic profile of a new anxiolytic, DN 2327 effect of R015-1788 and interaction with diazepam in rodents. Psychopharmacology 103 314-322, 1991... 

As the SCCE described above (Section 6.3.1.1) maybe part of a protein complex in the mitochondria, more effort was directed to study the possible interaction partners, especially the peripheral-t)q)e benzodiazepine receptor (PBR) (Papadopoulos et al, 1997 Koch, 2002) and the acyl-CoA-binding protein (ACBP Metzner et al, 2000). The ACBPs bind to the peripheral-t)q)e PBR present in the envelope of mitochondria (Gamier et al, 1994). This interaction stimulates the transport of cholesterol into mitochondria (Papadopoulos and Brown, 1995). The cholesterol taken up into the mitochondria is available as a substrate to the side-chain cleavage enzyme which transforms cholesterol into pregnenolone (Papadopoulos et al, 1997). Because of its interaction with PBR, ACBP is also described as diazepam-binding inhibitor or endozepine. Some isoforms of the latter were isolated and characterized from D. lanata (Metzner et al, 2000). Lindemann and Luckner (1997) speculated that cardenolide formation is regulated mainly by the availability of cholesterol and its transport into mitochondria, where the P450scc is assumed to be located. 

Compound 24 is a gamma-aminobutyric acid (GABA) receptor modulator that interacts with the GABA-A sub-type which is, in turn, the same locale where the classical benzodiazepine anxiolytics are also thought to interact (diazepam or Valium being a common benzodiazepine structure shown above as 57). Although 24 is classed as a nonbenzodiazepine sedative-hypnotic because it has... 

Those agents that interact with calcium channels but have another primary site of action include agents acting on sodium channels (local anesthetics and phenytoin), catecholamine receptors (benextramine, nicergoline, phenoxy-benzamine, phenothiazines, pimozide, propranolol, and yohimbine derivatives), benzodiazepine receptors (diazepam and flurazepam), opiate receptors (loperamide and flu-peramide), and cyclic nucleotide phosphodiesterases (amrinone, cromoglycate, and papaverine), as well as barbiturates, cyproheptadine, indomethacin, and reserpine. 

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