Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies.

Department of Psychiatry, University of Wuerzburg, Germany.
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.
Mesh Terms:
Aged, Binding, Competitive, Cerebral Cortex, Dizocilpine Maleate, Electrophysiology, Excitatory Amino Acid Antagonists, Female, Humans, In Vitro Techniques, Ion Channel Gating, Male, Membranes, Middle Aged, Muscarinic Antagonists, Neurons, Orphenadrine, Patch-Clamp Techniques, Receptors, N-Methyl-D-Aspartate, Receptors, Phencyclidine, Superior Colliculi
J. Neural Transm. Gen. Sect. Jan. 01, 1995; 102(3);237-46 [PUBMED:8788072]
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