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Research Area
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Description
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Neurological Disease |
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Biological Activity
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Description
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Galanthamine (Razadyne, Reminyl) is an AChE inhibitor with IC50 of 14 nM. |
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Targets
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AChE |
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IC50 |
14 nM [1] |
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In Vitro
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Galanthamine has been demonstrated to have an IC50 of 14 nM and 15 nM on AChE in post-mortem human brain frontal cortex and the hippocampus region. Red-cell cholinesterase activity in blood samples from the neurosurgery patients is 10 times more strongly inhibited by Galanthamine in brain tissue samples. [1] Galanthamine (1 μM) activates single channels with conductance’s of 18 and 30 pS in outside-out patches excised from dexamethasone mouse fibroblasts (M10 cells). [2] Galanthamine acts as ‘noncompetitive nicotinic receptor agonists’ on clonal rat pheochromocytoma (PC12) cells. Galanthamine (50 μM) activates single-channel currents in outside-out patches excised from clonal PC12 cells. [3] |
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In Vivo
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Galantamine significantly increases the number of living pyramidal neurons after ischemia-reperfusion injury. Galantamine significantly reduces TUNEL, active caspase-3, and SOD-2 immunoreactivity. The nicotinic antagonist mecamylamine blockes the protective effects of galantamine. The neuroprotective effects of galantamine are preserved even when first administered at 3 hours postischemia. [4] |
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Clinical Trials
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Galanthamine is now under the phase IV clinical trials for the efficacy and safety for improving dysfunction in people with bipolar disorder. |
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Features
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Protocol
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Kinase Assay
[1]
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| Acetylcholinesterase Assay |
The catalytic activity of acetylcholinesterase in erythrocytes and brain is measured using [14C]acetylcholine iodide radiolabelled in the acetyl moiety at a final substrate concentration of 3.6 mmM, a pH of 7.4 and a temperature of 25 °C. Concentration response trials are then performed. After incubation of the sample with Galanthamine for 60 minutes at 25 °C in vitro, the catalytic reaction is started by the addition of substrate. |
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Animal Study
[4]
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| Animal Models |
Gerbils |
| Formulation |
Galanthamine is dissolved in 0.9% NaCl saline solution. |
| Doses |
10 mg/kg |
| Administration |
S.c. twice a day or 3 or 6 hours after ischemia and at subsequent 12-hours intervals until sacrifice |
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References |
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[1] Thomsen T, et al. Eur J Clin Chem Clin Biochem, 1991, 29(8), 487-492.
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[2] Pereira EF, et al. J Pharmacol Exp Ther, 1994, 270(2), 768-778.
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[3] Storch A, et al. Eur J Pharmacol, 1995, 290(3), 207-219.
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[4] Lorrio S, et al. J Pharmacol Exp Ther, 2007, 322(2), 591-599.
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