Advertisement

Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 324, Issue 3, pp 235–237 | Cite as

The action of benzodiazepine antagonist Ro 15-1788 on the effects of GABA-ergic drugs

  • Lembit H. Allikmets
  • Lembit K. Rägo
Short Communication

Summary

The interaction of Ro 15-1788 (5 mg kg−1 i.p.), a benzodiazepine antagonist, with GABA-ergic drugs muscimol (1.4 mg kg−1 i.p.), fenibut (100 mg kg−1 i.p.) and baclofen (5 mg kg−1 i.p.) was examined in behavioural and biochemical studies in rats. All the above-mentioned GABA-ergic drugs produced motor depression and with the exception of muscimol, where anti-aggressive effect was evident, fenibut and baclofen showed only slight antiagressive properties. Ro 15-1788 attenuated the motor depression produced by these compounds but potentiated their antiaggressive effect. Moreover, it was found that Ro 15-1788 itself possessed dose-related antiagressive properties. Fenibut increased, whereas muscimol and Ro 15-1788 decreased, the GABA content in the rat striatum. Ro 15-1788 and all the studied GABA-ergic compounds increased the level of the dopaminc metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. In spite of this no further increase of DOPAC was observed after concomitant use of Ro 15-1788 with GABA-ergic drugs. The action of investigated GABA-ergic drugs via GABA receptors linked to benzodiazepine receptors is suggested.

Key words

Benzodiazepine antagonist Ro 15-1788 GABA-ergic drugs Interaction 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allikmets LH, Rägo LK, Nurk AM (1982) The influence of the GABA-receptor blockade on the effects of fenibut and diazepam. Bull Exp Biol Med 5:64–65Google Scholar
  2. De Feudis FV (1981) Muscimol binding and GABA receptors. Drug Dev Res 1:93–105Google Scholar
  3. Earley CJ, Leonard BE (1978) Isolation and assay of noradrenaline, dopamine, 5-hydroxytryptamine and several metabolites from brain tissue using disposable Bio-Rad columns packed with Sephadex G-10. J Pharmacol Meth 1:67–79Google Scholar
  4. Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain. J Neurochem 13:655–669Google Scholar
  5. Gundlach AL, Beart PM (1980) Effect of muscimol on dopamine metabolism of the rat hypothalamus. Experimentia 36:1312–1313Google Scholar
  6. Hill DR, Bowery NG (1981) 3H-Baclofen and 3H-GABA bind to bicuculline-insensitive GABAB sites in rat brain. Nature 290:149–152Google Scholar
  7. Hunkler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516Google Scholar
  8. Iversen LL, Spokes E, Bird E (1978) GABA systems in human brain Huntington's disease and schizophrenia. In: Neurotransmitters, vol 2. Advances in pharmacology and therapeutics. Proc. 7th International Congress of Pharmacology, Paris, pp 3–10Google Scholar
  9. Polc P, Laurent J-P, Scherschlicht R, Haefely W (1981) Electrophysiological studies on the specific benzodiazepine antagonist Ro 15-1788. Naunyn-Schmiedeberg's Arch Pharmacol 316:317–325Google Scholar
  10. Roberts PJ, Gupta HK, Shargill NS (1978) The interaction of baclofen (β-[4-chlorophenyl] GABA) with GABA systems in rat brain: evidence for a releasing action. Brain Res 155:209–214Google Scholar
  11. Rägo LK, Nurk AM, Korneyev AYa, Allikmets LH (1982) Fenibut binds to bicuculline insensitive GABA receptors in the rat brain. Bull Exp Biol Med 11:58–59Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Lembit H. Allikmets
    • 1
  • Lembit K. Rägo
    • 1
  1. 1.Department of PharmacologyTartu State UniversityTartuEstonia, USSR

Personalised recommendations