异氟磷辛对大鼠多巴胺D1和D2受体及行为的拮抗作用。

Antagonistic effects of isofloxythepin on dopamine D1 and D2 receptors and behaviors in rats.

Lau Y S, Fung Y K, Anderson T M

Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City 64108, USA.

Gen Pharmacol. 1997 Nov;29(5):729-36. doi: 10.1016/s0306-3623(97)00258-9.

Abstract

In vitro, isofloxythepin competed for the binding of [3H]SCH 23390 to striatal D1 receptors and for the binding of [3H]spiperone to striatal D2 receptors with IC50 values of 6.1 (+/- 1.2) x 10(-10)M and 8.4 (+/- 2.6) x 10(-10)M, respectively. Isofloxythepin further inhibited the D1 receptor-mediated, dopamine-stimulated adenylate cyclase in the striatal tissue. 2. Fifteen hours after rats were injected with a single dose of isofloxythepin (1 mg/kg, SC), the ex vivo binding curve of [3H]spiperone to striatal D2 receptors was markedly inhibited, whereas the binding curve of [3H]SCH 23390 to striatal D1 receptors was unaffected. 3. Fifteen hours after isofloxythepin pretreatment, D1 agonist SKF 38393 (15 mg/kg, IP)-stimulated grooming behavior was not affected, whereas the D2 agonist quinpirole (3 mg/kg, IP)-stimulated stereotyped behavior was completely abolished. 4. On the basis of the findings from in vivo studies, we conclude that, although isofloxythepin is found to have high affinity for both D1 and D2 receptors in vitro, it lacks D1 antagonistic potency in vivo.

摘要

在体外，异氟磷辛与[3H]SCH 23390竞争性结合纹状体D1受体，与[3H]螺哌隆竞争性结合纹状体D2受体，IC50值分别为6.1（±1.2）×10（-10）M和8.4（±2.6）×10（-10）M。异氟磷辛进一步抑制纹状体组织中D1受体介导的多巴胺刺激的腺苷酸环化酶。2. 大鼠单次注射异氟磷辛（1 mg/kg，皮下注射）15小时后，[3H]螺哌隆与纹状体D2受体的体外结合曲线受到显著抑制，而[3H]SCH 23390与纹状体D1受体的结合曲线未受影响。3. 异氟磷辛预处理15小时后，D1激动剂SKF 38393（15 mg/kg，腹腔注射）刺激的修饰行为未受影响，而D2激动剂喹吡罗（3 mg/kg，腹腔注射）刺激产生的刻板行为则完全被消除。4. 根据体内研究结果，我们得出结论，尽管异氟磷辛在体外对D1和D2受体均具有高亲和力，但在体内它缺乏D1拮抗效力。