Abstract:
:We investigated the ability of N-benzyl-N-ethyl-2-(7,8-dihydro-7-methyl-8-oxo-2-phenyl-9H-purin-9-yl)acetamide (AC-5216), a novel mitochondrial benzodiazepine receptor (MBR) ligand, to produce anti-anxiety and antidepressant-like effects in various animal models. AC-5216 showed high affinity for MBRs prepared from rat whole brain (Ki 0.297 nm), rat glioma cells (IC50 3.04 nm) and human glioma cells (IC50 2.73 nm), but only negligible affinity for the other main receptors including central benzodiazepine receptors. AC-5216 produced anti-anxiety effects in the Vogel-type conflict test in rats, and in the light/dark box and social interaction tests in mice at 0.1-3, 0.003-0.01 and 0.01-0.3 mg kg(-1), p.o., respectively. These effects of AC-5216 were antagonized by PK11195, an MBR antagonist. In the forced swimming test in rats, AC-5216 (3-30 mg kg(-1), p.o.) reduced the immobility time, and this effect was blocked by PK11195. AC-5216 had no myorelaxant effects, did not affect the memory or prolong hexobarbitone-induced sleep in mice, even at doses as high as 1000 mg kg(-1), p.o. Although it did slightly prolong the ethanol-induced sleep time at 1000 mg kg(-1), AC-5216 (1-100 mg kg(-1), p.o.) produced no distinct change in the rat electroencephalogram. These results indicate that AC-5216 produces anti-anxiety and antidepressant-like effects that are mediated by MBR, but does not cause the side effects normally associated with conventional benzodiazepines. Hence, AC-5216 shows potential for the treatment of stress-related disorders including anxiety and depression.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kita A,Kohayakawa H,Kinoshita T,Ochi Y,Nakamichi K,Kurumiya S,Furukawa K,Oka Mdoi
10.1038/sj.bjp.0705681subject
Has Abstractpub_date
2004-08-01 00:00:00pages
1059-72issue
7eissn
0007-1188issn
1476-5381pii
sj.bjp.0705681journal_volume
142pub_type
杂志文章abstract::1. The serine/threonine protein phosphatase (PP) inhibitors, okadaic acid and calyculin, attenuated the IgE-mediated release of histamine from human lung mast cells (HLMC) and basophils in a dose-dependent manner whereas an alternative PP inhibitor, microcystin, was ineffective. Calyculin was more potent than okadaic ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702169
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abstract:BACKGROUND AND PURPOSE:Chemokines and their receptors form an intricate interaction and signalling network that plays critical roles in various physiological and pathological cellular processes. The high promiscuity and apparent redundancy of this network makes probing individual chemokine/receptor interactions and fun...
journal_title:British journal of pharmacology
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doi:10.1111/bph.14132
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1995.tb16396.x
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1992.tb09049.x
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abstract::1. Murine left atrium lacks inotropic beta(2)-adrenoceptor function. We investigated whether beta(2)-adrenoceptors are involved in the cardiostimulant effects of (-)-adrenaline on spontaneously beating right atria and paced right ventricular myocardium of C57BL6 mice. We also studied a negative inotropic effect of (-)...
journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0704700
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1986.tb10177.x
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abstract::1. Simultaneous computer modelling of control and guanfacine-masked [3H]-MK 912 saturation curves as well as guanfacine competition curves revealed that the drugs bound to two alpha 2-adrenoceptor subtypes in the rat cerebral cortex with very different selectivities. These alpha 2-adrenoceptor subtypes were designated...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1992.tb14446.x
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1974.tb09591.x
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abstract::1. A series of opioid agonists, antagonists and their (+)-stereoisomers were tested for antiarrhythmic activity in the rat coronary artery occlusion model. 2. Naloxone (0.01-2 mg kg-1) significantly reduced the incidence and severity of cardiac arrhythmias, in accordance with previous published studies. 3. The non-opi...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1991.tb12235.x
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Down's syndrome is a common genetic cause of intellectual disability, for which there are no drug therapies. Mechanistic studies in a model of Down's syndrome [Ts65Dn (TS) mice] demonstrated that impaired cognitive function was due to excessive neuronal inhibitory tone. These deficits were normal...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12169
更新日期:2013-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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abstract::1. Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(-)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, live...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1983.tb10017.x
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更新日期:2017-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15520.x
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abstract::1. The variation with clock-hour in the behaviour of naive rats in a Y-maze has been recorded.2. The number of entries recorded was highest during the light period while the number of faecal boluses was highest during the dark period. Rearing showed a biphasic periodicity.3. The responses to LSD, mescaline and ampheta...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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abstract::1. The pharmacokinetics of cyclophosphamide were investigated in cancer patients. The data can be characterized by a two-compartment open model. The half life of the elimination phase of the drug ranged between 3 and 11 hours.2. Extensive tubular reabsorption of the drug resulted in the excretion of only a small perce...
journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1993.tb13727.x
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journal_title:British journal of pharmacology
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abstract:BACKGROUND AND PURPOSE:Red blood cells (RBCs) are reservoirs of vasodilatory, antiaggregatory, and antiinflammatory lipid mediators-epoxyeicosatrienoic acids (EETs). This study addresses the formation and release of erythrocyte-derived EETs in response to ATP receptor stimulation that may represent an important mechani...
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