(+)‐[3H]MK‐801 Binding Sites in Postmortem Human Brain
- 1 April 1990
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 54 (4) , 1163-1168
- https://doi.org/10.1111/j.1471-4159.1990.tb01944.x
Abstract
The pharmacological specificity and the regional distribution of the N-methyl-D-aspartate receptor-associated 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine maleate (MK-801) binding sites in human postmortem brain tissue were determined by binding studies using (+)-[3H]MK-801. Scatchard analysis revealed a high-affinity (KD= 0.9 ± 0.2 nM, Bmax= 499 ± 33 fmol/mg of protein) and a low-affinity (KD= 3.6 ± 0.9 nM, Bmax= 194 ± 44 fmol/ mg of protein) binding site. The high-affinity site showed a different regional distribution of receptor density (cortex > hippocampus > striatum) compared to the low-affinity binding site (cerebellum > brainstem). The rank order pharmacological specificity and stereoselectivity of the high-(cortex) and low-(cerebellar) affinity binding sites were identical. However, all compounds tested showed greater potency at the high-affinity site in cortex. The results indicate that (+)[3H]MK-801 binding in human postmortem brain tissue shows pharmacological and regional specificity.Keywords
This publication has 32 references indexed in Scilit:
- Synthesis and characterization of a radiolabelled derivative of the phencyclidine/N-methyl-D-aspartate receptor ligand (+)MK-801 with high specific radioactivityLife Sciences, 1988
- [3H]MK‐801 Labels a Site on the N‐Methyl‐D‐Aspartate Receptor Channel Complex in Rat Brain MembranesJournal of Neurochemistry, 1988
- Multiple mode of binding of phencyclidines: High affinity association between phencyclidine receptors in rat brain and a monovalent ion-sensitive polypeptideBiochemical and Biophysical Research Communications, 1987
- Phencyclidine (PCP) receptors: autoradiographic localization in brain with the selective ligand, [3H]TCPBrain Research, 1986
- Analysis of radioligand binding experimentsJournal of Pharmacological Methods, 1985
- Characterization of specific sigma opiate/phencyclidine (PCP)-binding sites in the human brainLife Sciences, 1983
- A practical computer-based approach to the analysis of radioligand binding experimentsComputer Programs in Biomedicine, 1983
- Anticonvulsant activity of (+)‐5‐methyl‐10, 11‐dihydro‐5H‐dibenzo[a, d]cyclohepten‐5, 10‐imine (MK‐801), a substance with potent anticonvulsant, central sympathomimetic, and apparent anxiolytic propertiesDrug Development Research, 1982
- On the Error of Counting with a HaemacytometerBiometrika, 1907