Effect of anesthetic and convulsant barbiturates on N-methyl-D-aspartate receptor-mediated calcium flux in brain membrane vesicles.

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Daniell LC

Effect of anesthetic and convulsant barbiturates on N-methyl-D-aspartate receptor-mediated calcium flux in brain membrane vesicles.

Pharmacology. 1994 Nov;49(5):296-307.

PubMed ID

7862741 [ View in PubMed

]

Abstract

The effects of anesthetic and convulsant barbiturates on brain N-methyl-D-aspartate (NMDA) receptor function were examined in a cell-free membrane vesicle preparation from mouse hippocampus. Increases in intracellular free calcium concentrations (Cai) were determined using a fluorescent dye, Indo-1, after stimulation with the NMDA receptor agonist, L-glutamate. Anesthetic barbiturates inhibited NMDA responses in a concentration-dependent manner with a rank order of potency of secobarbital > amobarbital > pentobarbital > mephobarbital = phenobarbital >> barbital. However, the IC50 values for these barbiturates were larger than probable blood anesthetic concentrations. Barbiturates with both anesthetic and convulsant effects in mice [optical isomers of pentobarbital and secobarbital, 5-(2-cyclohexylideneethyl)-5-ethylbarbituric acid and (+/-)-dimethylbutylbarbituric acid] also reduced NMDA responses. Inhibition of NMDA responses by racemic pentobarbital or isomers of pentobarbital was noncompetitive. Resting Cai was altered by all barbiturates tested except secobarbital and barbital, but not in a consistent manner, suggesting that the effect of barbiturates on resting Cai is not related either to their effects on NMDA receptor responses or to their behavioral effects. These results show that anesthetic and convulsant barbiturates inhibit NMDA responses, but their anesthetic and convulsant activities may be primarily due to their effects on other brain targets.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pentobarbital	NMDA receptor (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Phenobarbital	NMDA receptor (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Secobarbital	NMDA receptor (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details