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Titolo:
L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats
Autore:
Konieczny, J; Ossowska, K; Schulze, G; Coper, H; Wolfarth, S;
Indirizzi:
Polish,Acad Sci, Inst Pharmacol, Dept Neuropsychopharmacol, PL-31343 Krakow Polish Acad Sci Krakow Poland PL-31343 opsychopharmacol, PL-31343 Krakow Free Univ Berlin, Dept Clin Neurobiol, D-14050 Berlin, Germany Free Univ Berlin Berlin Germany D-14050 urobiol, D-14050 Berlin, Germany
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 3, volume: 143, anno: 1999,
pagine: 235 - 243
Fonte:
ISI
Lingua:
ENG
Soggetto:
EXCITATORY AMINO-ACIDS; D-ASPARTATE RECEPTORS; PARKINSONS-DISEASE; L-DOPA; MK-801; TONE; MEMANTINE; STRIATUM; SYMPTOMS; MODELS;
Keywords:
L-701,324; NMDA receptor; glycine site; muscle rigidity; catalepsy; rotarod; Parkinson's disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Konieczny, J PolishL-31343ci, Inst Pharmacol, Dept Neuropsychopharmacol, 12 Smetna St, P Polish Acad Sci 12 Smetna St Krakow Poland PL-31343 na St, P
Citazione:
J. Konieczny et al., "L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats", PSYCHOPHAR, 143(3), 1999, pp. 235-243

Abstract

Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson's disease. Therefore, a search for new compounds which block glutamatergicreceptors and show antiparkinsonian properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like muscle rigidity and catalepsy induced by haloperidol in rats. Methods: The muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior muscles. Results: L-701,324 (2.5-40 mg/kg IP) dose-dependently decreased the muscle tone enhanced by haloperidol (1-5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished byhigher doses of L-701,324. However, up to a dose of 20 mg/kg IF, L-701,324did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25-5 mg/kg IF) given alone or together with haloperidol (0.5-1mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits abeneficial action in the animal model of parkinsonian rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects.

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Documento generato il 18/01/20 alle ore 13:02:59