cgs-12066b and 9-10-dihydroergosine

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.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Animals; Antidepressive Agents; Binding, Competitive; Chlorpromazine; Ergotamines; Hippocampus; In Vitro Techniques; Male; Pindolol; Quinoxalines; Rats; Rats, Wistar; Receptors, Serotonin