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Phenytoin differentially modulates the affinity of agonist and antagonist ligands for σ 1 receptors of guinea pig brain
Author(s) -
Cobos Enrique J.,
Baeyens José M.,
Del Pozo Esperanza
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20103
Subject(s) - agonist , chemistry , allosteric regulation , antagonist , receptor , ligand (biochemistry) , pharmacology , intrinsic activity , guinea pig , partial agonist , inverse agonist , competitive antagonist , allosteric modulator , endocrinology , biochemistry , biology
We evaluated the effects of phenytoin (DPH) on the affinity for sigma‐1 (σ 1 ) receptors of agonist or antagonist σ 1 ligands in guinea pig brain. Heterologous competition experiments showed that DPH (250 μM and 1 mM) concentration‐dependently increased the affinity of the σ 1 agonists dextromethorphan, (+)‐SKF‐10,047, (+)‐3‐PPP, and PRE‐084. However, neither DPH 250 μM nor 1 mM increased (in fact, they slightly decreased) the affinity of the σ 1 receptor antagonists haloperidol, BD 1063, NE‐100, progesterone, and BD 1047. These findings suggest that allosteric modulation by DPH of the affinity of σ 1 receptor ligands depends on the agonist or antagonist characteristics of the ligand. Therefore, determining in vitro the differential modulation by DPH of σ 1 ligand affinity appears to constitute a procedure that can predict the pharmacological profile of different σ 1 ligands. Synapse 55:192–195, 2005. © 2005 Wiley‐Liss, Inc.