| Autor: |
Espallergues, J., Lapalud, P., Christopoulos, A., V. A.Avlani, Sexton, P. M., Vamvakides, A., Maurice, T. |
| Předmět: |
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| Zdroj: |
British Journal of Pharmacology; Sep2007, Vol. 152 Issue 2, p267-279, 13p, 1 Diagram, 1 Chart, 7 Graphs |
| Abstrakt: |
Background and purpose:Tetrahydro-N, N-dimethyl-5, 5-diphenyl-3-furanmethanamine hydrochloride (ANAVEX1-41) is a potent muscarinic and sigma1 (σ1) receptor ligand. The σ1 receptor modulates glutamatergic and cholinergic responses in the forebrain and selective agonists are potent anti-amnesic and antidepressant drugs. We have here analysed the σ1 component in the behavioural effects of ANAVEX1-41.Experimental approach:Binding of ANAVEX1-41 to muscarinic and σ1 receptors were measured using cell membranes. Behavioural effects of ANAVEX1-41 were tested in mice using memory (spontaneous alternation, passive avoidance, water-maze) and antidepressant-like activity (forced swimming) procedures.Key results:In vitro, ANAVEX1-41 was a potent muscarinic (M1>M3, M4>M2 with Ki ranging from 18 to 114 nM) and selective σ1 ligand (σ1, Ki=44 nM; σ2, Ki=4 μM). In mice, ANAVEX1-41 failed to affect learning when injected alone (0.03–1 mg kg−1), but attenuated scopolamine-induced amnesia with a bell-shaped dose response (maximum at 0.1 mg kg−1). The σ1 antagonist BD1047 blocked the anti-amnesic effect of ANAVEX1-41 on both short- and long-term memories. Pretreatment with a σ1 receptor-directed antisense oligodeoxynucleotide prevented effects of ANAVEX1-41 only in the passive avoidance procedure, measuring long-term memory. ANAVEX1-41 reduced behavioural despair at 30 and 60 mg kg−1, without involving the σ1 receptor, as it was not blocked by BD1047 or the antisense oligodeoxynucleotide.Conclusions and implications:ANAVEX1-41 is a potent anti-amnesic drug, acting through muscarinic and σ1 receptors. The latter component may be involved in the enhancing effects of the drug on long-term memory processes.British Journal of Pharmacology (2007) 152, 267–279; doi:10.1038/sj.bjp.0707386; published online 6 August 2007 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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