新しい抗うつ剤ロプラミンの行動薬理学的研究  [in Japanese] Behavioral pharmacology of lopramine  [in Japanese]

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Abstract

新しい三環性抗うつ薬lopramine(Leo640,DB-2182):N-methyl-N-(4-chlorobenzoylmethyl-3-(10,11-dihydro-5H-dibenz(b.f)azepin-5-yl)-propylamine hydrochlorideの行動薬理学的特性を,マウス,ラットを用いて検討し,imipramine,amitriptylineのそれと比較した.lopramine(LOP)は0.5%CMCに懸濁し,imipraminc(IMP),amitriptyline(AMT)は精製水に溶解し,特記しない限りは経口投与した.LOPはIMP,AMTと同様reserpine hypothermia,tetrabenazine ptosis,halopcridol catalepsyに拮抗し,methamphetamine,DOPAおよびapomorphineによる常同行動を増強する抗うつ薬としての薬理学的特性を有する.その他,LOPは中隔野破壊や嗅球摘出ラットの情動過多をIMP,AMTと同程度に抑制した.とくにmuricideは選択的に抑制され,嗅球摘出ラットのmuricide抑制作用のED50はLOP24,0,IMP39,0,AMT27.5mg/kgであった.一方Δ<SUP>9</SUP>-tetrahydrocannabinolによって起こるmuricide抑制作用のED50はLOP30.0,IMP14.5,AMT20mg/kg i.P.であった.LOPはIMP,AMTとは異なり5000mg/kgの大量でも軽度の鎮静を示す程度であり,―般活動性の増加およびmethamphetamine運動興奮の増強作用はIMP,AMTよりも強かった.またphysostigmineの致死作用やoxotremorine tremorを全く抑制しないので,LOPは中枢性抗コリン作用を欠くものと思われる.その他,5000mg/kgの大量でも協調運動障害や筋弛緩はみられず,死亡することもなかった.以上,LOPはIMPAMTに比べて一般活動性の増加,methamphetamine運動興奮の増強が強く,中枢性抗コリン作用はなく,しかも毒性の極めて少ない抗うつ薬と考えられる.

The behavioral effects of lopramine [N-methyl-N-(4-chlorobenzoyl-methyl)-3-(10, 11-dihydro-5H-dibenz (b, f) azepin-5-yl)propylamine hydrochloride] were investigated in mice and rats and compared with those of amitriptyline and imipramine. Lopramine inhibited reserpine hypothermia and haloperidol catalepsy in mice and tetrabenazine ptosis in rats. In addition, the drug potentiated the effects of methamphetamine, and DOPA or apomorphine-induced stereotypy in mice, whereas it suppressed muricide of the rat induced by either olfactory bulbectomy or Δ<SUP>9</SUP>-tetrahydrocannabinol, similar to the responses seen with imipramine and amitriptyline. On the other hand, lopramine increased spontaneous motor activity and markedly potentiated methamphetamine hyperactivity. In contrast to imipramine and amitriptyline, lopramine failed to counteract both the lethal effect of physostigmine and oxotremorine tremor in mice, indicating that the drug had no central anticholinergic effect. Lopramine, even at such a large dose as 5, 000 mg/kg p.o., caused neither impairment of coordinated motor activity nor muscle relaxation. It is concluded that lopramine is a new type of tricyclic antidepressant with extremely low toxicity and without central anticholinergic action.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 72(5), 585-607, 1976

    The Japanese Pharmacological Society

Cited by:  1

Codes

  • NII Article ID (NAID)
    130000758501
  • NII NACSIS-CAT ID (NCID)
    AN00198335
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    0015-5691
  • NDL Article ID
    1721374
  • NDL Source Classification
    SC351;SD0
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z19-247
  • Data Source
    CJPref  NDL  J-STAGE 
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