Involvement of serotonergic neuronal systems in the anti-amnesic action of naftidrofuryl oxalate.
The effects of naftidrofuryl oxalate on cycloheximide- and 5-hydroxytryptophan (5-HTP)-induced amnesia were investigated using a passive avoidance task in mice. Naftidrofuryl oxalate significantly improved the cycloheximide-induced amnesia. This effect of naftidrofuryl oxalate was antagonized by 5-HTP, a serotonin (5-HT) precursor, and by p-chloroamphetamine (PCA), a 5-HT releaser. Single administration of 5-HTP in combination with pargyline, a monoamine oxidase inhibitor, induced amnesia (5-HTP-induced amnesia). This amnesia was attenuated by ritanserin, a 5-HT2-selective antagonist, but not by pindolol, a 5-HT1-selective antagonist. Naftidrofuryl oxalate also attenuated the 5-HTP-induced amnesia. A binding study revealed that naftidrofuryl oxalate inhibited the binding of [3H]ketanserin to 5-HT2 receptors in mouse brain synaptic membrane in a dose-dependent fashion (IC50 = 1.42 x 10(-7) M), but did not inhibit that of [3H]serotonin to 5-HT1 receptors. These results suggest that naftidrofuryl oxalate may attenuate cycloheximide- and 5-HTP-induced amnesia by blocking 5-HT2 receptor subtypes.
Nabeshima
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Ichihara
K
K
Tohyama
K
K
Murase
K
K
Suzuki
T
T
Kameyama
T
T
D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003513:Cycloheximide / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009257:Nafronyl / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D009257:Nafronyl; D003513:Cycloheximide