L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats
| Autor: | Krystyna Ossowska, Jolanta Konieczny, Stanisław Wolfarth, G. Schulze, Helmut Coper |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Hindlimb Catalepsy Quinolones Receptors N-Methyl-D-Aspartate Muscle tone Internal medicine medicine Haloperidol Animals Parkinson Disease Secondary Rats Wistar Glycine receptor Pharmacology Chemistry Anti-Dyskinesia Agents Electromyography Antagonist medicine.disease Muscle Rigidity Rats Endocrinology medicine.anatomical_structure Anesthesia Muscle Tonus NMDA receptor Dopamine Antagonists Female Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Psychopharmacology. 143(3) |
| ISSN: | 0033-3158 |
| Popis: | 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 glutamatergic receptors 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 by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/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 a beneficial action in the animal model of parkinsonian rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects. |
| Databáze: | OpenAIRE |
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