SL 75 102 as a gama-aminobutyric acid agonist: experiments on dorsal root ganglion neurones in vitro.
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.
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*
D001640:Bicuculline; D002712:Chlorides; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C017984:progabide acid