ETHNOPHARMACOLOGICAL RELEVANCE Magnolia officinalis Rehder and Wilson [Magnoliaceae] bark and Ziziphus spinosa (Buhge) Hu ex. Chen. [Fam. Rhamnaceae] seed have a history of use in traditional Asian medicine for mild anxiety, nervousness and sleep-related problems. AIM OF THE STUDY To identify pharmacological targets, extracts of Magnolia officinalis (ME), Ziziphus spinosa (ZE), and a propriet...

Background: Despite introduction of modern antiepileptic drugs, 30% of epileptic patients are still drug resistant. Remarkable three-dimensional spatial structure of AdCA, yet the simplicity of the molecule, makes AdCA a promising lead compound. Methods: Sedative/motor impairment and 24-h mortality rate of AdCA were determined in mice. Impact of AdCA on (1) threshold and occurrence of clonic se...

Rhesus monkeys were trained to discriminate injections of saline from those of 8-carboline-3-carboxylic acid ethyl ester (8-CCE), a compound that binds to the benzodiazepine receptor, but often has actions opposite to those of the benzodiazeplnes. A benzodlazepine agonist midazolam and low doses of a specific benzodiazepine antagonist, Ro 15-1788, reversed the discriminative effects of 8-CCE. H...

The subcellular localization of central-type benzodiazepine receptors in bovine cerebral cortex, cerebellum, hippocampus, and corpus striatum has been studied. In all regions except for the corpus striatum, benzodiazepine receptors are most highly enriched in purified postsynaptic densities (PSDs) prepared by Triton X-100/hypotonic lysis of purified synaptosomal plasma membranes. Benzodiazepine...

The properties of GABA receptor-mediated responses were examined in noncultured astrocytes, acutely isolated from the mature rat hippocampus. Whole-cell patch clamping revealed a GABA-activated Cl- conductance that was mimicked by the GABAA receptor agonist muscimol and depressed by the GABAA antagonists bicuculline and picrotoxin. The GABAA-activated currents were potentiated by the barbiturat...

Benzodiazepine is an antixylotic agent , induce and maintain sleep, reduce seizures, and induce conscious sedation. It acts as a positive allosteric modulator of GABAA receptor. The binding of benzodiazepine analogues to this allosteric modulatory site enhances the affinity of GABA (Gama amino butyric acid) for the agonist recognition site. In the present work, docking studies has been performe...

In the development of non-radioactive receptor assays for benzodiazepines, employing fluorescent ligands, it was observed that the fluorescence measurements were hampered by the background fluorescence of the receptor preparation. This receptor preparation is a brain tissue homogenate in which the benzodiazepine receptors are membrane-bound. To minimize the influence of the receptor material on...

The acute and chronic effects of ramelteon, an MT1/MT2 receptor agonist, were evaluated in rhesus monkeys (Macaca mulatta) to assess discriminative stimulus effects in comparison with traditional benzodiazepine receptor agonists and to assess physical dependence potential. Discriminative effects of ramelteon were compared with midazolam in untreated monkeys and in diazepam-dependent monkeys tha...

muscle s, but 2-methylthioadenosine was a weak partial agonist. Furthermore, 8bromo substitution caused a loss of inhibitory activity in gut s and coronary smooth muscle ts. OI substituents may promote a syn conformation ill-suited for binding s'ts. However such a modification strongly shifts the parine dipole moment and reduces its strength s'ts. providing two possible explanations for loss of...

Benzodiazepine site agonists or inverse agonists enhance or reduce gamma-aminobutyric acid(A) (GABA(A)) receptor-mediated inhibition of neurons, respectively. Recently, it was demonstrated that the point mutation gamma 2F77I causes a drastic change in the affinity of a variety of benzodiazepine agonists or inverse agonists in receptor binding studies. Here we investigated the potency and effica...