An investigation into the potential mechanisms underlying the neuroprotective effect of clonidine in the retina

An investigation into the potential mechanisms underlying the neuroprotective effect of clonidine... α 2 -Adrenoceptor agonists, such as clonidine, attenuate hypoxia-induced damage to brain and retinal neurones by a mechanism of action which likely involves stimulation of α 2 -adrenoceptors. In addition, the neuroprotective effect of α 2 -adrenoceptor agonists in the retina may involve stimulation of bFGF production. The purpose of this study was to examine more thoroughly the neuroprotective properties of clonidine. In particular, studies were designed to ascertain whether clonidine acts as a free radical scavenger. It is thought that betaxolol, a β 1 -adrenoceptor antagonist, acts as a neuroprotective agent by interacting with sodium and L-type calcium channels to reduce the influx of these ions into stressed neurones. Studies were therefore undertaken to determine whether clonidine has similar properties. In addition, studies were undertaken to determine whether i.p. injections of clonidine or betaxolol affect retinal bFGF mRNA levels. In vitro data were generally in agreement that clonidine and bFGF counteracted the effect of NMDA as would occur in hypoxia. No evidence could be found that clonidine interacts with sodium or L-type calcium channels, reduces calcium influx into neurones or acts as a free radical scavenger at concentrations below 100 μM. Moreover, i.p. injection of clonidine, but not betaxolol, elevated bFGF mRNA levels in the retina. The conclusion from this study is that the neuroprotective properties of α 2 -adrenoceptor agonists, like clonidine, are very different from betaxolol. The fact that both betaxolol and clonidine blunt hypoxia-induced death to retinal ganglion cells suggests that combining the two drugs may be a way forward to producing more effective neuroprotection. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

An investigation into the potential mechanisms underlying the neuroprotective effect of clonidine in the retina

Brain Research, Volume 877 (1) – Sep 15, 2000

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science B.V.
ISSN
0006-8993
D.O.I.
10.1016/S0006-8993(00)02592-0
Publisher site
See Article on Publisher Site

Abstract

α 2 -Adrenoceptor agonists, such as clonidine, attenuate hypoxia-induced damage to brain and retinal neurones by a mechanism of action which likely involves stimulation of α 2 -adrenoceptors. In addition, the neuroprotective effect of α 2 -adrenoceptor agonists in the retina may involve stimulation of bFGF production. The purpose of this study was to examine more thoroughly the neuroprotective properties of clonidine. In particular, studies were designed to ascertain whether clonidine acts as a free radical scavenger. It is thought that betaxolol, a β 1 -adrenoceptor antagonist, acts as a neuroprotective agent by interacting with sodium and L-type calcium channels to reduce the influx of these ions into stressed neurones. Studies were therefore undertaken to determine whether clonidine has similar properties. In addition, studies were undertaken to determine whether i.p. injections of clonidine or betaxolol affect retinal bFGF mRNA levels. In vitro data were generally in agreement that clonidine and bFGF counteracted the effect of NMDA as would occur in hypoxia. No evidence could be found that clonidine interacts with sodium or L-type calcium channels, reduces calcium influx into neurones or acts as a free radical scavenger at concentrations below 100 μM. Moreover, i.p. injection of clonidine, but not betaxolol, elevated bFGF mRNA levels in the retina. The conclusion from this study is that the neuroprotective properties of α 2 -adrenoceptor agonists, like clonidine, are very different from betaxolol. The fact that both betaxolol and clonidine blunt hypoxia-induced death to retinal ganglion cells suggests that combining the two drugs may be a way forward to producing more effective neuroprotection.

Journal

Brain ResearchElsevier

Published: Sep 15, 2000

References

  • Presynaptic alpha2-adrenoceptors inhibit excitatory synaptic transmission in rat brain stem
    Bertolino, M.; Vicini, S.; Gillis, R.; Travagli, A.
  • Effects of clonidine and xylazine on body temperature in the rat
    Livingston, A.; Low, J.; Morris, B.
  • Neuroprotective strategies: voltage-gated Na + -channel down-modulation versus presynaptic glutamate release inhibition
    Obrenovitch, T.P.
  • Excitotoxic amino acids and neuropsychiatric disorders
    Olney, J.W.
  • In vivo and in vitro experiments show that betaxolol is a retinal neuroprotective agent
    Osborne, N.N.; Cazevieille, C.; Carvalho, A.L.; Larsen, A.K.; DeSantis, L.

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