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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1997-3-25
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pubmed:abstractText |
Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1). Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 microM which is nearly identical to the IC50 calculated at equilibrium.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
0300-9564
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
237-46
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:8788072-Aged,
pubmed-meshheading:8788072-Binding, Competitive,
pubmed-meshheading:8788072-Cerebral Cortex,
pubmed-meshheading:8788072-Dizocilpine Maleate,
pubmed-meshheading:8788072-Electrophysiology,
pubmed-meshheading:8788072-Excitatory Amino Acid Antagonists,
pubmed-meshheading:8788072-Female,
pubmed-meshheading:8788072-Humans,
pubmed-meshheading:8788072-Ion Channel Gating,
pubmed-meshheading:8788072-Male,
pubmed-meshheading:8788072-Membranes,
pubmed-meshheading:8788072-Middle Aged,
pubmed-meshheading:8788072-Muscarinic Antagonists,
pubmed-meshheading:8788072-Neurons,
pubmed-meshheading:8788072-Orphenadrine,
pubmed-meshheading:8788072-Patch-Clamp Techniques,
pubmed-meshheading:8788072-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:8788072-Receptors, Phencyclidine,
pubmed-meshheading:8788072-Superior Colliculi
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pubmed:year |
1995
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pubmed:articleTitle |
Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies.
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pubmed:affiliation |
Department of Psychiatry, University of Würzburg, Germany.
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pubmed:publicationType |
Journal Article,
In Vitro
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