SL 75 102 as a gama-aminobutyric acid agonist: experiments on dorsal root ganglion neurones in vitro

Br J Pharmacol. 1981 Feb;72(2):355-64. doi: 10.1111/j.1476-5381.1981.tb09135.x.

Abstract

1 In anticipation that centrally active gamma-aminobutyric acid (GABA)-mimetic drugs may be clinically useful, derivatives of GABA with an imine link (Schiff base) to a lipophilic carrier have recently been prepared. The present paper concerns the actions of [alpha(4-chlorophenyl)5-fluoro, 2-hydroxy benzilidene-amino]-4-butanoate Na+, SL 75 102. 2 To test one aspect of the GABA-mimetic properties of SL 75 102, this compound was compared with GABA for activity on intracellularly-recorded neurones in rat dorsal root ganglia in vitro. On these neurones GABA, administered either by microiontophoresis or direct into the superfusion medium, causes a depolarization, due to an increased chloride conductance, followed by a period of desensitization. 3 The actions of Sl 75 102 were in nearly all respects identical to those of GABA; parameters examined were the effects on membrane potential and input conductance, desensitization, dose-response characteristics and sensitivity to the GABA antagonists, bicuculline and picrotoxin. 4 SL 75 102 was less potent than GABA (mean relative potency 0.03:1). 5 SL 75 102 therefore appears to be a weak agonist at GABA receptors of these neurones.

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Chlorides / metabolism
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / drug effects*
  • Guinea Pigs
  • In Vitro Techniques
  • Neurons / drug effects*
  • Picrotoxin / pharmacology
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / pharmacology
  • gamma-Aminobutyric Acid / physiology*

Substances

  • Chlorides
  • Picrotoxin
  • gamma-Aminobutyric Acid
  • progabide acid
  • Bicuculline