The Effects of T-588, a Novel Cognitive Enhancer, on Noradrenaline Uptake and Release in Rat Cerebral Cortical Slices

Access this Article

Author(s)

Abstract

Previously, we reported that (<I>R</I>)-(-)-1-(benzo[<I>b</I>]thiophen-5-yl)-2-[2-(<I>N</I>, <I>N</I>-diethylamino)-ethoxy]ethanol hydrochloride (T-588), a novel cognitive enhancer, stimulated noradrenaline (NA) release from rat cerebral cortical slices. In this study, we investigated the effects of T-588 on NA uptake and release, compared to the effects of desipramine, a blocker of the NA carrier on the plasma membrane. Both T-588 and desipramine caused dose-dependent inhibition of [<SUP>3</SUP>H]NA uptake into the slices. Addition of 3 mM T-588 stimulated [<SUP>3</SUP>H]NA release from the prelabeled slices even in the presence of 10 μM desipramine, which inhibited NA uptake completely. Tyramine, which accelerates NA carrier-mediated release, also stimulated [<SUP>3</SUP>H]NA release, and tyramine-stimulated release was inhibited by desipramine. These findings indicated that T-588-stimulated NA release was not mediated by 1) inhibition of reuptake or 2) reverse transport mediated by NA carriers. Reserpine, which interacts with the intracellular vesicular transport system, increased [<SUP>3</SUP>H]NA efflux from slices. High K<SUP>+</SUP>-, not T-588-, stimulated [<SUP>3</SUP>H]NA release was shifted upward by reserpine. These findings suggest that T-588 evokes NA release by a mechanism similar to that induced by reserpine. T-588 might act as a cognitive enhancer via neurotransmitter release in the brain.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 77(2), 155-160, 1998-06-01

    The Japanese Pharmacological Society

References:  27

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008193015
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4514091
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
Page Top