Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand

British Journal of Pharmacology
Atsuko KitaMakoto Oka

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 ...Continue Reading

References

Feb 15, 1978·European Journal of Pharmacology·R D PorsoltM Jalfre
Jun 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·P GuarneriE Costa
Mar 1, 1989·Pharmacology, Biochemistry, and Behavior·B CostallD M Tomkins
Dec 1, 1987·Japanese Journal of Pharmacology·H ShimizuJ Katsube
Jan 1, 1986·Journal of Neurochemistry·A S Basile, P Skolnick
Mar 1, 1988·Pharmacology, Biochemistry, and Behavior·H Francès
Jan 1, 1971·Psychopharmacologia·J R VogelD E Clody
Jul 16, 1984·Life Sciences·S Pellow, S E File
Oct 1, 1993·Clinical Neuropharmacology·R Weizman, M Gavish
Feb 9, 2000·Frontiers in Neuroendocrinology·N A Compagnone, S H Mellon
Jul 15, 2000·Journal of Neuro-oncology·A Beurdeley-ThomasM F Poupon
Dec 13, 2000·Pharmacology, Biochemistry, and Behavior·R T KhistiS P Jain
Jun 22, 2001·Immunopharmacology and Immunotoxicology·R LazzariniJ Palermo-Neto
Dec 26, 2001·The Journal of Pharmacology and Experimental Therapeutics·H MöhlerU Rudolph
Feb 19, 2002·Neurochemistry International·Pierre CasellasAnthony S Basile

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Citations

Dec 2, 2010·Nature Reviews. Drug Discovery·Rainer RupprechtMichael Schumacher
Dec 13, 2006·Neuroendocrinology·Daniela EserRainer Rupprecht
Oct 2, 2008·European Journal of Nuclear Medicine and Molecular Imaging·Fabien ChauveauBertrand Tavitian
Mar 25, 2014·Expert Opinion on Therapeutic Targets·Giovana BristotAdriane R Rosa
Oct 18, 2011·Expert Opinion on Emerging Drugs·Giampaolo PernaDaniela Caldirola
Oct 31, 2006·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Rainer RupprechtHans-Jürgen Möller
Jul 21, 2015·Neuropharmacology·Katsukuni MitsuiSeishi Katsumata
Jun 6, 2009·Progress in Neuro-psychopharmacology & Biological Psychiatry·Atsuko KitaAkinori Akaike
Jan 19, 2008·Pharmacology, Biochemistry, and Behavior·Atsuko Kita, Kiyoshi Furukawa
Oct 13, 2015·Pharmacology, Biochemistry, and Behavior·Zhi-Kun QiuJi-Sheng Chen
Mar 13, 2008·The European Journal of Neuroscience·Charles MillsClifford J Woolf
Oct 22, 2011·British Journal of Pharmacology·Ashish Dhir, Michael A Rogawski
Oct 28, 2014·Brain Pathology·Guo-Jun LiuRichard B Banati
Jul 23, 2015·The Journal of Steroid Biochemistry and Molecular Biology·B D ArboM F Ribeiro
May 6, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Andrew S MidzakVassilios Papadopoulos
Jul 16, 2015·Journal of Medicinal Chemistry·Elisabetta BarresiClaudia Martini
Jul 17, 2016·The Journal of Endocrinology·Vimal Selvaraj, Lan N Tu
Jun 14, 2016·Clinical and Experimental Pharmacology & Physiology·Qiang ChengMing-Gao Zhao
Jan 12, 2016·Scientific Reports·Barbara CostaClaudia Martini
Jan 20, 2016·Journal of Psychopharmacology·Li-Ming ZhangYun-Feng Li

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