Possible antidepressant dihydroergosine preferentially binds to 5-HT1B receptor sites in the rat hippocampus.
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.
Muck-Seler
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Laboratory for Molecular Neuropharmacology, Ruder Bosković Institute, Zagreb, Croatia.
Pericić
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D004879:Ergotamines / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*
D000928:Antidepressive Agents; D004879:Ergotamines; D011810:Quinoxalines; D011985:Receptors, Serotonin; C052561:CGS 12066B; C037580:9,10-dihydroergosine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; D002746:Chlorpromazine