The Antidepressant Metapramine is a Low-affinity Antagonist at N -methyl- d -aspartic Acid Receptors
| Autor: | Frangoise Bordier, Adam Doble, Alain Boireau, Gabrielle Durand |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Receptor complex
Glycine Phencyclidine N-Methyl-D-aspartic acid Antidepressive Agents Tricyclic In Vitro Techniques Pharmacology Binding Competitive Receptors N-Methyl-D-Aspartate Cellular and Molecular Neuroscience chemistry.chemical_compound Dibenzazepines medicine Animals Receptor Cyclic GMP Cerebral Cortex Binding Sites Cell Membrane Antagonist Rats Inbred Strains Rats chemistry Mechanism of action NMDA receptor Metapramine Dizocilpine Maleate medicine.symptom |
| Zdroj: | Neuropharmacology. 35:1703-1707 |
| ISSN: | 0028-3908 |
| DOI: | 10.1016/s0028-3908(96)00122-0 |
| Popis: | Metapramine, a pharmacological compound with antidepressant activity in humans, was tested for possible antiglutamatergic activity, in vitro. We investigated the effects of metapramine on the N-methyl-d-aspartic acid (NMDA) receptor complex, by determining whether this compound would interfere with the binding of [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) to rat cortical membranes in the presence of either glycine NMDA, or both. Metapramine in the micromolar range inhibited the binding of [3H]TCP in the presence of both NMDA and glycine (ic50 = 1.4 ± 0.2 μM). That very similar affinities were observed when either NMDA or glycine was present suggests that metapramine exerted a direct action at the PCP site. The affinity of metapramine for this site was about 25 and 350 times lower than that of PCP and MK-801, respectively. Metapramine inhibited the NMDA-evoked increase in guanosine 3′,5′-cyclic monophosphate (cGMP) levels of neonatal rat cerebellar slices (ic50 = 13 μM). These results suggest that metapramine is a low-affinity antagonist of the NMDA receptor complex channel. This paper discusses the potential application of metapramine to the treatment of diseases linked to excessive stimulation of glutamatergic NMDA receptors. © 1997 Elsevier Science Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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