Sustained facilitatory action of FK960 on hippocampal neurotransmission.
The present study investigated the effect of N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a piperazine derivative developed as antidementia drug, on hippocampal neurotransmission. FK960 increased the amplitude of population spikes (PSs) from the granular cell layer in rat hippocampal slices in a bell-shaped dose-dependent manner at concentrations ranged from 10 nM to 10 microM. A similar potentiation was found in the intact mouse hippocampus, the action being still evident 120 min after injection; a maximal effect was obtained with 3 mg/kg intraperitoneal injection of FK960 at concentrations ranged from 0.3 to 5 mg/kg. The facilitatory action induced by FK960 did not occlude the potentiation induced by tetanic stimulation. The results of the present study indicate that FK960 induces a long-lasting facilitation of hippocampal neurotransmission, but by a mechanism independent of the tetanic long-term potentiation. This may account for the memory enhancing action of FK960.
Matsuyama
S
S
Department of Pharmacology, Kobe University School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-ku, Kobe, Japan.
Nomura
T
T
Nishizaki
T
T
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D001549:Benzamides; C102991:N-(4-acetyl-1-piperazinyl) -4-fluorobenzamide monohydrate; D018697:Nootropic Agents; D010879:Piperazines