Anti‐amnesic effect of dimemorfan in mice

• Published in: British journal of pharmacology 2003-03, Vol.138 (5), p.941-949
• Main Authors: Wang, Hui‐Hung, Chien, Jyh‐Wei, Chou, Yueh‐Ching, Liao, Jyh‐Fei, Chen, Chieh‐Fu
• Format: Article
• Language: English
• Subjects: (+)‐SKF‐10047; Amnesia - chemically induced; Amnesia - drug therapy; Amyloid beta-Peptides - toxicity; Animals; anti‐amnesic effect; Avoidance Learning - drug effects; Avoidance Learning - physiology; Biological and medical sciences; Dimemorfan; Dose-Response Relationship, Drug; haloperidol; Male; Medical sciences; Mice; Mice, Inbred ICR; Morphinans - pharmacology; Morphinans - therapeutic use; Peptide Fragments - toxicity; Phenazocine - analogs & derivatives; Phenazocine - pharmacology; Phenazocine - therapeutic use; Receptors, sigma - agonists; Receptors, sigma - physiology; scopolamine; Scopolamine Hydrobromide - toxicity; step‐through passive avoidance; water maze; β‐amyloid peptide‐(25‐35); σ1 receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705117

Dimemorfan, an antitussive for more than 25 years, has previously been reported to be a relative high‐affinity ligand at sigma‐1 (σ1) receptor with the Ki value of 151 nM. To test whether dimemorfan has anti‐amnesic effects similar to a σ1 receptor agonist, this study examined its effects on scopolamine‐ and β‐amyloid peptide‐(25‐35)‐induced amnesia in mice. Dimemorfan (10–40 mg kg−1, i.p.) administered 30 min before the training trial, immediately after the training trial, or 30 min before the retention test significantly improved scopolamine (1 mg kg−1, i.p.)‐ or β‐amyloid peptide‐(25‐35) (3 nmol mouse−1, i.c.v.)‐induced amnesia in a step‐through passive avoidance test. Dimemorfan (5–40 mg kg−1, i.p.) pretreatment also attenuated scopolamine (8 mg kg−1, i.p.)‐induced amnesia in a water‐maze test. And, these anti‐amnesic effects of dimemorfan, like the putative σ1 receptor agonist (+)‐N‐allylnormetazocine ((+)‐SKF‐10047), were antagonized by a σ receptor antagonist haloperidol (0.25 mg kg−1, i.p.). These results indicated that dimemorfan has anti‐amnesic effects and acts like a σ1 receptor agonist. British Journal of Pharmacology (2003) 138, 941–949. doi:10.1038/sj.bjp.0705117