[Effects of fluvoxamine on both the desired anxiolytic effect and the adverse motor incoordination and amnesia induced by benzodiazepines].
Fluvoxamine, a selective serotonin reuptake inhibitor, is frequently used along with benzodiazepine anxiolytics in clinics. In this study, the effects of fluvoxamine on the anxiolytic effects as well as adverse effects of benzodiazepines were examined in the light/dark box, rota-rod and passive avoidance tests using mice. Diazepam, ethyl loflazepate and its active metabolite, CM7116, were used as benzodiazepine anxiolytics. The anxiolytic effects of diazepam, ethyl loflazepate and CM7116 were potentiated by intraperitoneal treatment with fluvoxamine at 10 mg/kg, whereas only those of ethyl loflazepate were potentiated by fluvoxamine at 45 mg/kg. The motor incoordination and amnesia induced by ethyl loflazepate and CM7116 were not affected by fluvoxamine, although these adverse effects of diazepam were potentiated by fluvoxamine at 45 mg/kg. Fluvoxamine itself showed no effects in any of the tests. These results suggest that low-dose fluvoxamine potentiates the anxiolytic effects of benzodiazepines, while high-dose fluvoxamine augments the adverse effects depending on the benzodiazepine used. Consequently, when fluvoxamine is administered along with benzodiazepines, the doses of both fluvoxamine and benzodiazepines should be carefully chosen to achieve anxiolytic effects without any adverse results.
Imanishi
T
T
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-8567, Japan.
Onozawa
K
K
Hayashi
A
A
Baba
J
J
D000647:Amnesia / Q000139:chemically induced*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D001259:Ataxia / Q000139:chemically induced*; D001569:Benzodiazepines; D003975:Diazepam / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D016666:Fluvoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D003975:Diazepam; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors; C029617:ethyl loflazepate