Deramciclane improves object recognition in rats: potential role of NMDA receptors.
The cognition-enhancing properties of deramciclane (N,N-dimethyl-2-([(1R,4R,6S)-1,7,7-trimethyl-6-phenyl-6-bicyclo[2.2.1]heptanyl]oxy)ethanamine) and memantine (3,5-dimethyl-tricyclo[3.3.1.1(3,7)]decylamine-3,5-dimethyladamantan-1-amine) were evaluated in the novel object recognition (OR) test in the rat, while their effect in comparison with other N-methyl-D-aspartate (NMDA) receptor blockers such us MK-801 ([+]-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate) and CPP ([+/-]-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid) on NMDA-evoked spreading depression (SD) was investigated in the chicken retina, in vitro. In the OR test, pretreatment of rats with either deramciclane (30 mg/kg p.o.) or memantine (10 and 30 mg/kg, p.o.) resulted in preference for the novel object, compared to the familiar one, indicating procognitive activity of the compounds. In the in vitro studies memantine (10-30 M), or deramciclane (30-100 M) as well as CPP (0.1-1 M), MK-801 (0.3-1 M), concentration-dependently inhibited NMDA evoked SD. Furthermore, the inhibitory effect of memantine, deramciclane and MK-801 was activity-dependent. These results support the role of NMDA receptors in the procognitive effect of deramciclane.
Kertész
Szabolcs
S
Division of Preclinical Research, EGIS Pharmaceuticals Plc., Budapest, Hungary.
Kapus
Gábor
G
Gacsályi
István
I
Lévay
György
G
D000818:Animals; D001892:Camphanes / Q000494:pharmacology*; D002645:Chickens; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008559:Memantine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000502:physiology
D001892:Camphanes; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C060555:deramciclane; D008559:Memantine