POSSIBLE ANTIDEPRESSANT DIHYDROERGOSINE PREFERENTIALLY BINDS TO 5-HT(1B) RECEPTOR-SITES IN THE RAT HIPPOCAMPUS

The binding affinity of a possible antidepressant drug, dihydroergosin e, for various 5-HT1 receptor subtypes was studied in the hippocampal rat brain membranes. Dihydroergosine displaced the binding of [H-3]5-H T to the whole population of hippocampal 5-HT1 receptors with high aff inity (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 (+/-) pindol ol (1 muM) were included to block 5-HT1A + 5-HT1C, 5-HT1B + 5-HT1C, an d 5-HT1A + 5-HT1B receptor subtype respectively, the competition studi es have shown that under these selective conditions dihydroergosine bi nds with the highest affinity for 5-HT1B (Ki = 0.48 nM), with 8.7 time s 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 r eceptors, this study suggests that the high affinity of this drug for 5-HT1B receptors should not be neglected.