| Abstrakt: |
1 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. 2 AC-5216 showed high affinity for MBRs prepared from rat whole brain (K, 0.297nM), rat glioma cells (IC50 3.04nM) and human glioma cells (IC50 2.73nM). but only negligible affinity for the other main receptors including central benzodiazepine receptors. 3 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 0.01-0.3mg kg-1, p.o., respectively. These effects of AC-5216 were antagonized by PK 11195, an MBR antagonist. In the forced swimming test in rats, AC-5216 (3-30mg kg-1 , p.o.) reduced the immobility time, and this effect was blocked by PK 11195. 4 AC-5216 had no rnyorelaxant effects, did not affect the memory or prolong hexobarbitone-induced sleep in mice, even at doses as high as 1000mg kg-1, p.o. Although it did slightly prolong the ethanol-induced sleep time at l000mg kg-1, AC-5216 (1-100mg kg-1, p.o.) produced no distinct change in the rat electroencephalogram. 5 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. [ABSTRACT FROM AUTHOR] |
