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Titolo:
COMPARATIVE PATCH-CLAMP STUDIES WITH FRESHLY DISSOCIATED RAT HIPPOCAMPAL AND STRIATAL NEURONS ON THE NMDA RECEPTOR ANTAGONISTIC EFFECTS OF AMANTADINE AND MEMANTINE
Autore:
PARSONS CG; PANCHENKO VA; PINCHENKO VO; TSYNDRENKO AY; KRISHTAL OA;
Indirizzi:
MERZ & CO,DEPT PHARMACOL,ECKENHEIMER LANDSTR 100-104 D-60318 FRANKFURT 1 GERMANY UKRAINIAN ACAD SCI,AA BOGOMOLETZ INST PHYSIOL,DEPT CELLULAR MEMBRANOLKIEV 252024 UKRAINE
Titolo Testata:
European journal of neuroscience
fascicolo: 3, volume: 8, anno: 1996,
pagine: 446 - 454
SICI:
0953-816X(1996)8:3<446:CPSWFD>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
BASAL GANGLIA; GLUTAMATE; CHANNEL; BLOCK; ACID; ACETYLCHOLINE; RESPONSES; INVITRO; RELEASE; BRAIN;
Keywords:
CONCENTRATION CLAMP; (+)-MK-801; KETAMINE; KINETICS; AMPA; GABA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
C.G. Parsons et al., "COMPARATIVE PATCH-CLAMP STUDIES WITH FRESHLY DISSOCIATED RAT HIPPOCAMPAL AND STRIATAL NEURONS ON THE NMDA RECEPTOR ANTAGONISTIC EFFECTS OF AMANTADINE AND MEMANTINE", European journal of neuroscience, 8(3), 1996, pp. 446-454

Abstract

Patch- and concentration-clamp techniques were used to compare the effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists (+)-MK-801 (dizocilpine, (+)-5-methyl-10,11-dihydro-5H-dibenzo cyclohepten-5,10-imine maleate), ketamine, memantine (1-amino-3,5-dimethyladamantane) and amantadine (1-amino-adamantane) on agonist-induced inward currents in freshly dissociated rat hippocampal and striatal neurons. In hippocampal neurons, ketamine (5 mu M), memantine (10 mu M) and amantadine (100 mu M) selectively antagonized inward current responses to NMDA (500 gamma M plus glycine 5 mu M) in a voltage-dependent manner without affecting responses to lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (100 mu M) or gamma-aminobutyric acid (10 mu M). The NMDA receptor antagonistic effect of all four agents was typical of open channel blockade. The kinetics of blockade/unblockade was inversely related to antagonist affinity. In hippocampal neurons amantadine was the least potent NMDA receptor antagonist (IC50 18.6 +/- 0.9 mu M) and showed the fastest blocking kinetics, whereas (+)-MK-801 was the most potent (IC50 0.12 +/- 0.01 mu M) and showed the slowest blocking kinetics. Memantine (IC50 1.04 +/- 0.26 mu M) and ketamine (IC50 0.43 +/- 0.10 mu M) were almost equipotent and had similar, intermediate blocking kinetics. In striatal neurons recorded under identical conditions (+)-MK-801, ketamine and memantine were 3- to 4-fold less potent whereas amantadine was somewhat more potent than on hippocampal neurons. This could offer an explanation for the better clinical profile of amantadine in Parkinson's disease, as therapeutically relevant concentrations of amantadine are likely to be more active in the striatum whereas memantine is likely to be more active in other structures.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 17:13:05