[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)].
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.
Vamvakidès
A
A
Laboratoire de pharmacologie expérimentale, Faculté de médecine d'Athènes, Athènes, Grèce.
Antoniou
K
K
Daïfoti
Z
Z
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology
C482878:3, 4'-dihydro-N,N-dimethylspiro (9H-fluorene-9,2' (5'H)-furane)-3'-methanamine; D000927:Anticonvulsants; D003292:Convulsants; D005663:Furans; D018727:Muscarinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D013141:Spiro Compounds; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D000547:Amantadine; D010433:Pentylenetetrazole