Muck-Seler D, Pericić D
Laboratory for Molecular Neuropharmacology, Ruder Bosković Institute, Zagreb, Croatia.
J Neural Transm Gen Sect. 1993;92(1):1-9. doi: 10.1007/BF01245157.
The binding affinity of a possible antidepressant drug, dihydroergosine, for various 5-HT1 receptor subtypes was studied in the hippocampal rat brain membranes. Dihydroergosine displaced the binding of [3H]5-HT to the whole population of hippocampal 5-HT1 receptors with high affinity (Ki = 4.8 nM). The displacement curve was shallow and the slope factor less than unity, suggesting the interaction of dihydroergosine with multiple binding sites. When 8-OH-DPAT (100 nM) + chlorpromazine (500 nM), CGS 12066 B (200 nM) + ritanserin (500 nM), and (+/-)pindolol (1 microM) were included to block 5-HT1A + 5-HT1C, 5-HT1B + 5-HT1C, and 5-HT1A + 5-HT1B receptor subtype respectively, the competition studies have shown that under these selective conditions dihydroergosine binds with the highest affinity for 5-HT1B (Ki = 0.48 nM), with 8.7 times lower affinity for 5-HT1A (Ki = 4.2 nM) and with a moderate affinity for 5-HT1C (Ki = 156 nM) receptor subtype. While our previous studies suggested that dihydroergosine stimulates 5-HT1A and inhibits 5-HT2 receptors, this study suggests that the high affinity of this drug for 5-HT1B receptors should not be neglected.
在大鼠脑海马体膜中研究了一种可能的抗抑郁药物双氢麦角碱对各种5-HT1受体亚型的结合亲和力。双氢麦角碱以高亲和力（Ki = 4.8 nM）取代了[3H]5-HT与整个海马体5-HT1受体群体的结合。置换曲线较平缓，斜率因子小于1，表明双氢麦角碱与多个结合位点相互作用。当加入8-OH-DPAT（100 nM）+氯丙嗪（500 nM）、CGS 12066 B（200 nM）+利坦色林（500 nM）和（+/-）吲哚洛尔（1 μM）分别阻断5-HT1A + 5-HT1C、5-HT1B + 5-HT1C和5-HT1A + 5-HT1B受体亚型时，竞争研究表明，在这些选择性条件下，双氢麦角碱对5-HT1B的结合亲和力最高（Ki = 0.48 nM），对5-HT1A的亲和力低8.7倍（Ki = 4.2 nM），对5-HT1C受体亚型具有中等亲和力（Ki = 156 nM）。虽然我们之前的研究表明双氢麦角碱刺激5-HT1A并抑制5-HT2受体，但这项研究表明该药物对5-HT1B受体的高亲和力不容忽视。
