Ichimaru Y, Egawa T, Sawa A
Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., Yokohama, Japan.
Jpn J Pharmacol. 1995 May;68(1):65-70. doi: 10.1254/jjp.68.65.
The effect of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, was studied in a model of anxiety and/or obsessive compulsive disorder (OCD) in mice. In the anxiety/OCD model, marble-burying behavior, marble-burying was significantly suppressed by fluvoxamine at 30 and 60 mg/kg, p.o. and the monoamine reuptake inhibitor clomipramine, at 60 mg/kg, p.o. No suppressive effect, however, was observed by the selective norepinephrine reuptake inhibitor desipramine at doses from 15 to 60 mg/kg, p.o. Suppressive effects were obtained by the serotonergic anxiolytic buspirone at 30 and 60 mg/kg, p.o. and the benzodiazepine anxiolytic diazepam at 10 mg/kg, p.o. The effect of fluvoxamine on marble-burying was slightly attenuated after repeated administration. On the other hand, both the effects of buspirone and diazepam completely disappeared after repeated administration. Effect of fluvoxamine on the marble-burying was unaffected by the 5-HT2 antagonist ritanserin. However, the 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine) inhibited the suppressive effect of fluvoxamine on the marble-burying. From these results, the 5-HT1A-receptor subtype may be involved in the suppressive effect of fluvoxamine on the marble-burying, but the 5-HT2-receptor subtype is not involved in this effect.
在小鼠焦虑和/或强迫症(OCD)模型中研究了选择性5-羟色胺(5-HT)再摄取抑制剂氟伏沙明的作用。在焦虑/OCD模型中,氟伏沙明以30和60mg/kg口服给药时,大理石埋藏行为显著受到抑制,单胺再摄取抑制剂氯米帕明以60mg/kg口服给药时也有此作用。然而,选择性去甲肾上腺素再摄取抑制剂地昔帕明在15至60mg/kg口服给药剂量时未观察到抑制作用。5-羟色胺能抗焦虑药丁螺环酮以30和60mg/kg口服给药以及苯二氮䓬类抗焦虑药地西泮以10mg/kg口服给药均获得了抑制作用。重复给药后,氟伏沙明对大理石埋藏的作用略有减弱。另一方面,丁螺环酮和地西泮的作用在重复给药后完全消失。氟伏沙明对大理石埋藏的作用不受5-HT2拮抗剂利坦色林的影响。然而,5-HT1A拮抗剂NAN-190(1-(2-甲氧基苯基)-4-[4-(2-邻苯二甲酰亚胺基)丁基]哌嗪)抑制了氟伏沙明对大理石埋藏的抑制作用。从这些结果来看,5-HT1A受体亚型可能参与了氟伏沙明对大理石埋藏的抑制作用,但5-HT2受体亚型不参与此作用。