Dihydroergotamine

Dihydroergotamine (DFN-19) is a blood-brain barrier-permeable semi-synthetic ergot alkaloid, acting as a full agonist of 5-HT1B/1D receptors (K_i values of 0.3 nM and 2.5 nM, respectively; functional IC₅₀ values of 2 nM and 2.2 nM, respectively). Dihydroergotamine inhibits Forskolin (HY-15371)-stimulated cAMP accumulation, possesses α-adrenergic receptor antagonistic activity and weak dopaminergic agonistic activity. It mediates intracranial cerebrovascular contraction, inhibits the release of neuropeptides such as CGRP/substance P, and suppresses neurogenic inflammation by activating 5-HT1B/1D receptors in the trigeminovascular system. Dihydroergotamine binds to the catalytic site of Trypanosoma cruzi trypanothione reductase and exhibits trypanocidal activity in vitro. Dihydroergotamine can be used in studies related to migraine and trypanosome infections^[1][2][3][4]. In Vitro:Dihydroergotamine binds with high affinity to human 5-HT1B receptors in butyrate-treated HEK293 cells (K_i = 0.3 nM), human 5-HT1B receptors in mIFNβ-induced L929sA cells (K_i = 0.5 nM), and human 5-HT1D receptors in butyrate-treated C6 glioma cells (K_i = 0.7 nM)^[1].
Dihydroergotamine (20 min) fully inhibits Forskolin (HY-15371)-stimulated cAMP accumulation in L929sA and HEK 293 cells expressing human 5-HT₁B receptors, with IC₅₀ values of 0.4 nM and 2.0 nM, respectively^[1].
Dihydroergotamine (20 min) completely inhibits Forskolin-stimulated cyclic AMP accumulation in mIFNβ-induced L929sA cells expressing human 5-HT₁B receptors, with an IC₅₀ of 0.4 nM^[1].
Dihydroergotamine (20 min) completely inhibits Forskolin (IC₅₀ = 2.2 nM)- and isoproterenol-stimulated cyclic AMP accumulation in C6 glioma cells expressing the human 5-HT₁D receptor^[1].
Dihydroergotamine (0.01-1 μM; 24 h) mesylate protects Neuro-2a neuronal cells against oxygen-glucose deprivation-induced injury, with a significant increase in cell viability observed^[3].
Dihydroergotamine binds to the catalytic site of Trypanosoma cruzi trypanothione reductase, with a docking score of -9.536 kcal/mol^[4].
Dihydroergotamine (6.25-100 μg/mL; 24 h) exhibits an LC₅₀ of 28.1 μM against the trypomastigote form of Trypanosoma cruzi strain NINOA and an LC₅₀ of 57 μM against strain INC-5 in vitro, showing superior trypanocidal activity compared with reference trypanocidal drugs^[4]. In Vivo:Dihydroergotamine (617 mg/kg; lower unspecified doses) induces 50% embryonic mortality in rats, while lower doses cause structural congenital malformations^[2].
Dihydroergotamine (10 mg/kg/day; i.p.; daily; 14 days) improves survival, neurological function, and reduces brain injury in MCAO mice by inhibiting pro-inflammatory cytokine production and promoting microglial/macrophage polarization toward the neuroprotective M2 phenotype^[3].
Dihydroergotamine (100 mg/kg; single dose) mesylate reduces blood parasite survival to 62.44% at 8 hours post-administration in a short-term murine model of acute Chagas disease, with less efficacy than benznidazole^[4].