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N-methyl-D-aspartate and alpha 2-adrenergic mechanisms are involved in the depressant action of flupirtine on spinal reflexes in rats.

Abstract：

:In urethane-chloralose anesthetised rats the muscle relaxant activity of flupirtine was investigated on the monosynaptic Hoffmann reflex recorded from plantar foot muscles and on the polysynaptic flexor reflex recorded from tibialis muscle. Intraperitoneal (i.p.; 2.5-25 mumol/kg) and intrathecal (i.t.; 33-330 nmol) administration of flupirtine depressed the polysynaptic flexor reflex in anesthetised rats in a dose-dependent manner without affecting the monosynaptic Hoffmann reflex. Flupirtine produced a similar pattern on spinal reflexes as NMDA receptor antagonists, such as (-)-2-amino-7-phosphonoheptanoic acid (500 nmol i.t.) and memantine (125 mumol/kg i.p.), the benzodiazepines diazepam (18 mumol/kg i.p.) and midazolam (80 nmol i.t.), and the alpha 2-adrenoceptor agonist tizanidine (2 mumol/kg). In contrast, the GABAA receptor agonist muscimol (21 mumol/kg i.p.; 20 nmol i.t.) and the GABAB receptor agonist baclofen (47 mumol/kg i.p.; 2 nmol i.t.) reduced the magnitude of both the flexor and the Hoffmann reflex, whereas the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX; 10 nmol i.t.) depressed the Hoffmann reflex without affecting the flexor reflex. The effect of i.t. injection of flupirtine was prevented by coadministration of the mixed alpha 1/alpha 2-adrenoceptor antagonist yohimbine (10 nmol) and the excitatory amino acid N-methyl-D-aspartate (NMDA; 0.1 nmol), but neither by coadministration of the alpha 1-adrenoceptor antagonist prazosine (10 nmol), the GABAA receptor antagonist bicuculline (1 nmol), the GABAB receptor antagonist phaclofen (100 nmol), the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionic acid (ATPA; 0.1 pmol) nor by pre-treatment with the benzodiazepine receptor antagonist flumazenil (16 mumol/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Schwarz M,Schmitt T,Pergande G,Block F

doi

10.1016/0014-2999(95)00043-k

subject

Has Abstract

pub_date

1995-04-04 00:00:00

pages

247-55

issue

eissn

0014-2999

issn

1879-0712

pii

001429999500043K

journal_volume

276

pub_type

杂志文章

在线工具

N-methyl-D-aspartate and alpha 2-adrenergic mechanisms are involved in the depressant action of flupirtine on spinal reflexes in rats.