Central effects of nicotinamide and inosine which are not mediated through benzodiazepine receptors

Br J Pharmacol. 1985 Mar;84(3):689-96. doi: 10.1111/j.1476-5381.1985.tb16151.x.

Abstract

The actions of nicotinamide and inosine were investigated on rat cerebellar Purkinje cells using ionophoretic and extracellular recording techniques. Ionophoretic application of nicotinamide or inosine showed that they were potent inhibitors of Purkinje cell firing. This inhibition differed from that induced by benzodiazepines in that it was not reversed by the GABA antagonists bicuculline methiodide and picrotoxin. RO 15-1788, the specific benzodiazepine antagonist, did not reverse the effects of nicotinamide. Chlordiazepoxide has been shown to increase significantly social interaction between pairs of male rats and this increase can be reversed by RO 15-1788, 20 mg kg-1 i.p. Nicotinamide also caused a small increase in social interaction but this effect was not reversed by the benzodiazepine antagonist. Inosine did not increase social interaction. [3H]-flunitrazepam binding studies showed that nicotinamide and inosine have only low affinities for the benzodiazepine binding site. These results suggest that while nicotinamide may exert some neuronal depressant and anxiolytic activity, its site of action appears not to be associated with the benzodiazepine receptor site. Similarly, inosine exerts a neuronal depressant effect dissimilar from that of benzodiazepines.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Benzodiazepinones / pharmacology
  • Bicuculline / pharmacology
  • Binding, Competitive / drug effects
  • Brain / metabolism
  • Chlordiazepoxide / pharmacology
  • Convulsants / pharmacology
  • Female
  • Flumazenil
  • Flunitrazepam / metabolism
  • In Vitro Techniques
  • Inosine / pharmacology*
  • Male
  • Membranes / metabolism
  • Niacinamide / pharmacology*
  • Purkinje Cells / drug effects*
  • Purkinje Cells / physiology
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / physiology
  • Social Behavior

Substances

  • Benzodiazepinones
  • Convulsants
  • Receptors, GABA-A
  • Niacinamide
  • Flumazenil
  • Inosine
  • Flunitrazepam
  • Chlordiazepoxide
  • Bicuculline