N-Methyl-d-aspartate and α2-adrenergic mechanisms are involved in the depressent action of flupirtine on spinal reflexes in rats

摘要: In urethane-chloralose anesthetised rats the muscle relaxant activity of flupirtine was investigated on monosynaptic Hoffmann reflex recorded from plantar foot muscles and polysynaptic flexor tibialis muscle. Intraperitoneal (i.p.; 2.5–25 μmol/kg) intrathecal (i.t.; 33–330 nmol) administration depressed in a dose-dependent manner without affecting reflex. Flupirtine produced similar pattern spinal reflexes as NMDA receptor antagonists, such (−)-2-amino-7-phosphonoheptanoic acid (500 nmol i.t.) memantine (125 μmol/kg i.p.), benzodiazepines diazepam (18 i.p.) midazolam (80 i.t.), α2-adrenoceptor agonist tizanidine (2 μmol/kg). contrast, GABAA muscimol (21 i.p.; 20 GABAB baclofen (47 2 reduced magnitude both reflex, whereas non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 The effect i.t. injection prevented by coadministration mixed α1α2-adrenoceptor yohimbine (10 excitatory amino N-methyl-d-aspartate (NMDA; 0.1 nmol), but neither α1-adrenoceptor prazosine bicuculline (1 phaclofen (100 α-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionic (ATPA; pmol) nor pre-treatment with benzodiazepine flumazenil (16 These observations suggest that α2-adrenoceptors receptors might be involved mediation flupirtine. presumed antagonistic would particular clinical relevance, since is free typical side effects antagonists.