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Mécanisme d’action des effets anticonvulsivant et anti-immobilité (nage forcée) de la 3’, 4’-dihydro-N, N-diméthylspiro [9H-fluorène-9, 2’ (5’H)- furane] - 3’-méthanamine (AE37F)

Authors
  • Vamvakidès, A.
  • Antoniou, K.
  • Daïfoti, Z.
Type
Published Article
Journal
Annales Pharmaceutiques Françaises
Publisher
Elsevier
Publication Date
Jan 01, 2004
Volume
62
Issue
1
Pages
49–55
Identifiers
DOI: 10.1016/S0003-4509(04)94281-2
Source
Elsevier
Keywords
License
Unknown

Abstract

AE37F, a new aminotetrahydrofuranic derivative, exhibited, at 10-30mg/Kg (po) or 1-10mg/Kg (ip), antagonism of tonic convulsions, induced by pentetrazole (130mg/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 itsantimuscarinic properties, b) that the rate of 5-HT release in the NRPO, calculated here bya new approach (from the 5-HT and 5-HIAA brain levels), is increased by AE37Fand decreased by amantadine, in the NRPO, c) that the anticonvulsant action, observed with AE37F, could berelated to a NMDA-sigma mediated stimulation of serotoninergic, GABAergic andglycinergic brain neurones, antagonized by the NMDA-sigma inhibition induced by amantadine.

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