Publications by authors named "C Wollenburg"

The fact that potent NMDA receptor channel blockers produce phencyclidine-like psychotropic symptoms in man and rodents implies that uncompetitive antagonism of NMDA receptors may not be a promising therapeutic approach. However, recent data indicate that agents with moderate affinity such as memantine and neramexane (MRZ 2/579) are useful therapeutics due to their strong voltage-dependency and rapid unblocking kinetics. Merz has developed a series of novel uncompetitive NMDA receptor antagonists based on an amino-alkylcyclohexane structure.

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Although the concentration of drugs in brain homogenates is relatively easy to determine, such data are sometimes misleading due to accumulation in intracellular compartments. This is apparent for uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists where concentrations assessed in this manner are much higher than those sufficient to block the NMDA channel from the extracellular space. The aim of the present study was to determine whether free brain concentrations (extracellular fluid - ECF) of a new uncompetitive NMDA receptor antagonist MRZ 2/579 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride) following administration of doses effective in animal models are sufficient to block NMDA receptors based on its potency in vitro.

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Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites.

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A series of novel tricyclic pyrido-phthalazine-dione derivatives was tested for antagonistic effects at the strychnine-insensitive modulatory site of the N-methyl-D-aspartate (NMDA) receptor (glycineB). All compounds displaced [3H]MDL-105,519 binding to rat cortical membranes with IC50 values of between 90 nM and 3.6 microM.

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