Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice

D'HOOGE, R ; RAES, A ; et al.

In: Arzneimittel-Forschung, Jg. 48 (1998), Heft 12, S. 1121-1125

academicJournal - print, 20 ref

The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 127910-31-0, 4-methyl-APPA. CGP 37849) and its ethyl ester (CAS 127910-32-1, CGP 39551) potently block NMDA-evoked whole-cell current on mouse spinal neurones in primary dissociated cell cultures with IC50 (± SE) values of 189 ± 9 nmol/l (CGP 37849) and 2100 ± 220 nmol/l (CGP 39551), respectively. The compounds dose-dependently blocked vestibular stimulation-induced convulsions in EL mice, 2 h after oral administration, with ED50 (95% CI) values of 135 (78-236) μmol/kg (CGP 37849) and 65 (45-94) μmol/ kg (CGP 39551). In male Swiss albino mice, performance in the step-through passive avoidance procedure was dose-dependently impaired with ED50 (95% CI) values of 85 (56-157) μmol/kg (CGP 37849) and 27 (18-42) μmol/kg (CGP 39551). In addition performance of these animals in the rotarod test of motor coordination was impaired. h after oral administration of CGP 39551, with an ED50 (95% CI) of 142 ( 100-201) μmol/kg. These findings demonstrate anticonvulsant activity in these potent NMDA antagonists after oral administration with CGP 39551 possessing greater relative potency. However, the unfavourable ratio of therapeutic dose versus dose inducing memory or motor impairment supports the prevailing notion that such adverse effects of the presently available compounds preclude the use of NMDA antagonists as long-term therapies.

Titel:	Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice
Autor/in / Beteiligte Person:	D'HOOGE, R ; RAES, A ; HIRAMATSU, M ; MORI, A ; VAN BOGAERT, P.-P ; DE DEYN, P. P
Link:	View record from PASCAL Archive
Zeitschrift:	Arzneimittel-Forschung, Jg. 48 (1998), Heft 12, S. 1121-1125
Veröffentlichung:	Aulendorf: Cantor, 1998
Medientyp:	academicJournal
Umfang:	print, 20 ref
ISSN:	0004-4172 (print)
Schlagwort:	Pharmacology drugs Pharmacologie, galénique Sciences biologiques et medicales Biological and medical sciences Sciences medicales Medical sciences Pharmacologie. Traitements medicamenteux Pharmacology. Drug treatments Neuropharmacologie Neuropharmacology Anticonvulsivants. Antiépileptiques. Antiparkinsoniens Anticonvulsants. Antiepileptics. Antiparkinson agents Encéphale pathologie Cerebral disorder Encéfalo patología Mammalia Rodentia Système nerveux central pathologie Central nervous system disease Sistema nervosio central patología Système nerveux pathologie Nervous system diseases Sistema nervioso patología Vertebrata Antagoniste Antagonist Antagonista Anticonvulsivant Anticonvulsant Anticonvulsivante Culture cellulaire Cell culture Cultivo celular Effet biologique Biological effect Efecto biológico Epilepsie Epilepsy Epilepsia In vitro In vivo Modèle animal Animal model Modelo animal Moelle épinière Spinal cord Médula espinal Neurone Neuron Neurona Neurophysiologie Neurophysiology Neurofisiología Potentiel évoqué Evoked potential Potencial evocado Relation dose réponse Dose activity relation Relación dosis respuesta Récepteur NMDA NMDA receptor Receptor NMDA Souris Mouse Ratón Toxicité Toxicity Toxicidad CGP 37849 CGP 39551
Sonstiges:	Nachgewiesen in: PASCAL Archive Sprachen: English Original Material: INIST-CNRS Document Type: Article File Description: text Language: English Author Affiliations: Laboratory of Neurochemistry and Behaviour, Born-Bunge Foundation, and Department of Neurology - Memory Clinic, Middelheim General Hospital, University of Antwerp (UIA), Antwerp, Belgium ; Laboratory of Electrobiology, Born-Bunge Foundation, University of Antwerp (RUCA), Antwerp, Belgium ; Division of Medical Science, Institute for Life Support Technology, Yamagata Technopolis Foundation, Yamagata, Japan ; Department of Molecular and Cell Biology, University of California at Berkeley, California, United States Rights: Copyright 1999 INIST-CNRS ; CC BY 4.0 ; Sauf mention contraire ci-dessus, le contenu de cette notice bibliographique peut être utilisé dans le cadre d’une licence CC BY 4.0 Inist-CNRS / Unless otherwise stated above, the content of this bibliographic record may be used under a CC BY 4.0 licence by Inist-CNRS / A menos que se haya señalado antes, el contenido de este registro bibliográfico puede ser utilizado al amparo de una licencia CC BY 4.0 Inist-CNRS Notes: Pharmacological treatments ; Psychopathology. Psychiatry. Clinical psychology

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