Uses
LY-344864 Hydrochloride is used as a selective 5-HTIF receptor agonist.
Biological Activity
Potent, selective 5-HT 1F receptor agonist (EC 50 = 3 nM). Displays > 80-fold selectivity over other 5-HT receptors (K i values are 0.006, 0.53, 0.55, 0.56, 1.42, 1.70, 3.50, 3.94 and 4.85 μ M for 5-HT 1F , 5-HT 1A , 5-HT 1B , 5-HT 1D , 5-HT 1E , 5-HT 2B , 5-HT 2C , 5-HT 2A and 5-HT 7 receptors respectively). Inhibits neurogenic dural inflammation in vivo following i.v. and oral administration.
in vivo
LY 344864 (0-10 ng/kg; p.o. or i.v.; once) inhibits neurogenic dural inflammation in rat migraine pain model[1].
LY 344864 (1 mg/kg; i.v.; once) can cross the blood brain barrier to some extent in rats[1].
LY 344864 (2 mg/kg; i.p.; daily for 14 days) attenuates dopaminergic neuron loss and improved behavioral endpoints in a Parkinson’s disease mouse model[2].
| Animal Model: | Male Wistar rats, migraine pain model[1] |
| Dosage: | 1-10 ng/kg (oral), 0.3-2 ng/kg (intravenous) |
| Administration: | Oral, 75 minutes before trigeminal stimulation or intravenous, 10 minutes before trigeminal stimulation |
| Result: | When given intravenously 10 minutes before stimulation, inhibited inflammation with an ID50 (median infective dose) of 0.6 ng/kg. When administered orally 75 minutes before trigeminal stimulation, an ID50 of 1.2 ng/kg was obtained. |
| Animal Model: | Male C57BL/6 mice, Parkinson’s disease model[2] |
| Dosage: | 2 mg/kg |
| Administration: | Intraperitoneal injection, daily for 14d beginning 7d post-lesion |
| Result: | Attenuated TH-ir loss in the striatum and substantia nigra compared to vehicle-treated lesioned animals, also increased locomotor activity in 6-hydroxydopamine lesioned mice, while vehicle treatment had no effect. |
IC 50
human 5-HT
1F Receptor: 0.006 μM (Ki); human 5-HT
1A Receptor: 0.530 μM (Ki); human 5-HT
1B Receptor: 0.549 μM (Ki); human 5-HT
1D Receptor: 0.575 μM (Ki); human 5-HT
1E Receptor: 1.415 μM (Ki); human 5-HT
2B Receptor: 1.695 μM (Ki); Human 5-HT
2A Receptor: 3.499 μM (Ki); Human 5-HT
3A Receptor: 3.935 mM (Ki); Human 5-HT
7 Receptor: 4.851 μM (Ki); rat α2-adrenergic receptor: 3.69 μM (Ki); rat α1-adrenergic receptor: 5.06 μM (Ki)
