Anti‐amnesic effect of dimemorfan in mice

Dimemorfan, an antitussive for more than 25 years, has previously been reported to be a relative high‐affinity ligand at sigma‐1 (σ 1 ) receptor with the K i value of 151 n M . To test whether dimemorfan has anti‐amnesic effects similar to a σ 1 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 σ 1 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 σ 1 receptor agonist.British Journal of Pharmacology (2003) 138 , 941–949. doi: 10.1038/sj.bjp.0705117