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Neuroprotective Effects of Some Monoamine Oxidase‐B Inhibitors Against DSP‐4‐Induced Noradrenaline Depletion in the Mouse Hippocampus
Author(s) -
Yu P. H.,
Davis B. A.,
Fang J.,
Boulton A. A.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63051820.x
Subject(s) - neuroprotection , pharmacology , desipramine , chemistry , monoamine oxidase , in vivo , monoamine oxidase b , axon , hippocampus , hippocampal formation , biochemistry , antidepressant , biology , endocrinology , neuroscience , enzyme , microbiology and biotechnology
DSP‐4 [ N ‐(2‐chloroethyl)‐ N ‐ethyl‐2‐bromobenzylamine], a selective noradrenaline (NA) uptake blocker, is capable of inducing long‐lasting depletion of NA in some noradrenergic axon terminals and of subsequently causing cell death to NA neuronal cell bodies in rodents. R (−)‐Deprenyl, a selective monoamine oxidase (MAO)‐B inhibitor, has been shown to be capable of protecting animals against this DSP‐4‐induced neuronal degeneration. Its action, however, has been claimed to be unrelated to the inhibition of MAO‐B activity but rather due to competition for the NA uptake sites. The effects of several types of MAO inhibitors against DSP‐4 toxicity, MAO‐B activity both in vivo and in vitro, and NA uptake into the hippocampus have been assessed. N ‐(2‐Hexyl)‐ N ‐methylpropargylamine (2‐HxMP), a potent MAO‐B inhibitor, for example, exerts no appreciable effect on NA uptake but is quite potent in counteracting the NA‐depleting effect of DSP‐4. Such results rule out the possibility that the neuroprotective effect of the MAO‐B inhibitors is due mainly to their effect on NA uptake. The in vitro inhibition of MAO‐B activity seems to correlate positively with their neuroprotective effects against DSP‐4. In comparison to the MAO‐B inhibitors, NA uptake blockers, such as desipramine and S (+)‐deprenyl, exhibit relatively low efficacy in protecting the NA axon terminals from the effects of DSP‐4‐induced damage. The restoration of hippocampal NA levels is significantly enhanced with repeated treatments of R (−)‐deprenyl or 2‐HxMP even at very low doses following the DSP‐4 insult. This suggests that in addition to neuroprotection, these MAO‐B inhibitors may rescue some of the noradrenergic axon terminals damaged by DSP‐4.