• Archives of Pharmacal Research
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• v.23 no.1
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• pp.31-34
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• 2000

An efficient procedure for the preparation of 7,8-dichloro-6-nitro-1H-1,5-benzodiazepine-2,4-(3H, 5H)-dione(7) as a potential lead compound for the NMDA receptor glycine binding site antagonist, starting from readily available 4,5-dichloro-2-nitroaniline(8), is described. The key step in the synthesis involves the cyclization of malonic ester amide 10 to compound 11.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.166-171
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• 2007

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.769-774
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• 1997

Non-neuronal high affinity binding sites for benzodiazepines have been found in many peripheral tissues including cardiac muscle and vascular smooth muscle, and have been designated as 'peripheral benzodiazepine receptor'. Benzodiazepines have been shown to induce relaxation of the ileal, vesical, and uterine smooth muscles. However, it is still unclear about possible involvement of peripheral benzodiazepine receptor on the contractility of trachealis muscle. This study was performed to investigate the role of the peripheral benzodiazepine receptor on the contractility of canine trachealis muscle. Canine trachealis muscle strips of 15 mm long were suspended in an isolated organ bath containing 1 ml of physiological salt solution maintained at $37^{\circ}C$, and aerated with $95%\;O_2/5%\;CO_2$. Isometric myography was performed, and the results of the experiments were as follows: Ro5-4684, FGIN-1-27 and clonazepam reduced a basal tone of isolated canine trachealis muscle strip concentration dependently, relaxant actions of RoS-4684 and FGIN-1-27 were antagonized by PK11195, a peripheral benzodiazepine receptor antagonist. Flumazenil, a central type antagonist, did not antagonize the relaxant action of Peripheral type agonists. Saturation binding assay of [3H]Ro5-4864 showed a high affinity$(Kd=5.33{\pm}1.27nM,\;Bmax=\;867.3{\pm}147.2\;fmol/mg\;protein)$ binding site on the canine trachealis muscle. Ro 5-4684 suppressed the bethanechol-, 5-hydroxyoyptamine- and histamine- induced contractions. Platelet activating factor (PAF) exerted strong and prolonged contraction in trachealis muscle strip. Strong tonic contraction by PAE was attenuated by Ro 5-4684, but not by WEB 2086, a PAF antagonist. Based on these results, it is concluded that the peripheral benzodiazepine receptor mediates the inhibitory regulation of contractilty of canine trachealis muscle.

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.120-120
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• 2005