Anti-amnesic effect of dimemorfan in mice.
(1) Dimemorfan, an antitussive for more than 25 years, has previously been reported to be a relative high-affinity ligand at sigma-1 (sigma(1)) receptor with the K(i) value of 151 nM. (2) To test whether dimemorfan has anti-amnesic effects similar to a sigma(1) receptor agonist, this study examined its effects on scopolamine- and beta-amyloid peptide-(25-35)-induced amnesia in mice. (3) 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 beta-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 sigma(1) receptor agonist (+)-N-allylnormetazocine ((+)-SKF-10047), were antagonized by a sigma receptor antagonist haloperidol (0.25 mg kg(-1), i.p.). (4) These results indicated that dimemorfan has anti-amnesic effects and acts like a sigma(1) receptor agonist.
Wang
Hui-Hung
HH
Department & Institute of Pharmacology, National Yang-Ming University, No. 155, Sec. 2, Li-Nong Street, Taipei 112, Taiwan.
Chien
Jyh-Wei
JW
Chou
Yueh-Ching
YC
Liao
Jyh-Fei
JF
Chen
Chieh-Fu
CF
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009019:Morphinans / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000633:toxicity; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017480:Receptors, sigma / Q000819:agonists / Q000502:physiology; D012601:Scopolamine / Q000633:toxicity
D016229:Amyloid beta-Peptides; D009019:Morphinans; D010446:Peptide Fragments; D017480:Receptors, sigma; C074636:amyloid beta-protein (25-35); C012621:dimemorfan; C012134:SK&F 10047; D012601:Scopolamine; D010620:Phenazocine