[Action mechanism of anticonvulsant and anti-immobility (forced swim) effects of 3', 4'-dihydro-N, N-dimethylspiro-[9H-fluorene-9, 2' (5'H) furane]-3'-methanamine (AE37F)]

Ann Pharm Fr. 2004 Jan;62(1):49-55. doi: 10.1016/s0003-4509(04)94281-2.
[Article in French]

Abstract

AE37F, a new aminotetrahydrofuranic derivative, exhibited, at 10-30 mg/Kg (po) or 1-10 mg/Kg (ip), antagonism of tonic convulsions, induced by pentetrazole (130 mg/Kg, ip), and of forced swin immobility, in mice. At these doses AE37F induced a considerable (100-250%) increase of serotonin (5-HT) and its main metabolite, 5-hydroxyindolacetic acid (5-HIAA), in the rat nucleus reticularis pontis oralis (NRPO), antagonized by amantadine, which also increased 5-HT and 5-HIAA levels in the NRPO. It is suggested: a) that the anti-immobility effect of AE37F is related to its antimuscarinic properties, b) that the rate of 5-HT release in the NRPO, calculated here by a new approach (from the 5-HT and 5-HIAA brain levels) is increased by AE37F and decreased by amantadine, in the NRPO, c) that the anti-convulsant action, observed with AE37F, could be related to a NMDA-sigma mediated stimulation of serotoninergic, GABAergic and glycinergic brain neurones, antagonized by the NMDA-sigma inhibition induced by amantadine.

Publication types

  • English Abstract

MeSH terms

  • Amantadine / pharmacology
  • Animals
  • Anticonvulsants / pharmacology*
  • Brain Chemistry / drug effects
  • Convulsants / pharmacology
  • Furans / pharmacology*
  • Hydroxyindoleacetic Acid / metabolism
  • Mice
  • Motor Activity / drug effects
  • Muscarinic Antagonists / chemical synthesis
  • Muscarinic Antagonists / pharmacology
  • Pentylenetetrazole / antagonists & inhibitors
  • Pentylenetetrazole / pharmacology
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Serotonin / metabolism
  • Spiro Compounds / pharmacology*
  • Swimming / psychology

Substances

  • 3, 4'-dihydro-N,N-dimethylspiro (9H-fluorene-9,2' (5'H)-furane)-3'-methanamine
  • Anticonvulsants
  • Convulsants
  • Furans
  • Muscarinic Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Spiro Compounds
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Amantadine
  • Pentylenetetrazole