Cobos Enrique J, Baeyens José M, Del Pozo Esperanza
Department of Pharmacology and Institute of Neuroscience, School of Medicine, University of Granada, 18012 Granada, Spain.
Synapse. 2005 Mar 1;55(3):192-5. doi: 10.1002/syn.20103.
We evaluated the effects of phenytoin (DPH) on the affinity for sigma-1 (sigma(1)) receptors of agonist or antagonist sigma(1) ligands in guinea pig brain. Heterologous competition experiments showed that DPH (250 microM and 1 mM) concentration-dependently increased the affinity of the sigma(1) agonists dextromethorphan, (+)-SKF-10,047, (+)-3-PPP, and PRE-084. However, neither DPH 250 microM nor 1 mM increased (in fact, they slightly decreased) the affinity of the sigma(1) receptor antagonists haloperidol, BD 1063, NE-100, progesterone, and BD 1047. These findings suggest that allosteric modulation by DPH of the affinity of sigma(1) receptor ligands depends on the agonist or antagonist characteristics of the ligand. Therefore, determining in vitro the differential modulation by DPH of sigma(1) ligand affinity appears to constitute a procedure that can predict the pharmacological profile of different sigma(1) ligands.
我们评估了苯妥英（DPH）对豚鼠脑内σ-1（σ(1)）受体激动剂或拮抗剂σ(1)配体亲和力的影响。异源竞争实验表明，DPH（250μM和1 mM）浓度依赖性地增加了σ(1)激动剂右美沙芬、(+)-SKF-10,047、(+)-3-PPP和PRE-084的亲和力。然而，250μM和1 mM的DPH均未增加（实际上，它们略有降低）σ(1)受体拮抗剂氟哌啶醇、BD 1063、NE-100、孕酮和BD 1047的亲和力。这些发现表明，DPH对σ(1)受体配体亲和力的变构调节取决于配体的激动剂或拮抗剂特性。因此，在体外确定DPH对σ(1)配体亲和力的差异调节似乎构成了一种可以预测不同σ(1)配体药理学特征的方法。
