(1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.0^{1,12}.0^{6,17}]heptadeca-6,8,10(17),15-tetraen-14-ol hydrobromide

• ChemBase ID: 72627
• Molecular Formular: C17H22BrNO3
• Molecular Mass: 368.26548
• Monoisotopic Mass: 367.07830557
• SMILES: c12c3c(ccc1CN(CC[C@]12[C@@H](O3)C[C@H](C=C1)O)C)OC.Br
• Canonical SMILES: COc1ccc2c3c1O[C@@H]1[C@@]3(CCN(C2)C)C=C[C@@H](C1)O.Br
• InChI: InChI=1S/C17H21NO3.BrH/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17;/h3-6,12,14,19H,7-10H2,1-2H3;1H/t12-,14-,17-;/m0./s1
• InChIKey: QORVDGQLPPAFRS-XPSHAMGMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.0^{1,12}.0^{6,17}]heptadeca-6,8,10(17),15-tetraen-14-ol hydrobromide; (1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.0^1,^1^2.0^6,^1^7]heptadeca-6,8,10(17),15-tetraen-14-ol hydrobromide
• IUPAC Traditional name: galantamine hydrobromide
• Synonyms: GALANTHIAMIN HBR; Reminyl; Galanthamine hydrobromide; Galantamine hydrobromide; Galanthamine hydrobromide from Lycoris sp.

Database IDs

• CAS Number: 1953-04-4; 69353-21-5
• EC Number: 217-780-5
• MDL Number: MFCD00067672
• PubChem SID: 162037552; 24895074
• PubChem CID: 121587

CALCULATED PROPERTIES

• Acid pKa: 14.810377
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): -1.9891269
• LogD (pH = 7.4): -0.35530484
• Log P: 1.1630428
• Molar Refractivity: 82.3049 cm^3
• Polarizability: 31.647512 Å^3
• Polar Surface Area: 41.93 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C
• RTECS: DF8075000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3
• Risk Statements: 25
• Safety Statements: 45
• GHS Pictograms: GHS06
• GHS Signal Word: Danger
• GHS Hazard statements: H301
• GHS Precautionary statements: P301 + P310
• Personal Protective Equipment: Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 3
• Storage Temperature: -20°C

Pharmacology Properties

• Target: mAChRs mAChRs

Product Information

• Purity: ≥94% (TLC)
• Salt Data: Hydrobromide

DETAILS

MP Biomedicals - 05209140

MP Biomedicals Rare Chemical collection

Selleck Chemicals - S1339

Research Area

• Description: Neurological Disease

Biological Activity

• Description: Galanthamine (Razadyne, Reminyl) is an AChE inhibitor with IC50 of 14 nM.
• Targets: AChE
• IC50: 14 nM ^[1]
• In Vitro: 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]
• In Vivo: 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]
• Clinical Trials: Galanthamine is now under the phase IV clinical trials for the efficacy and safety for improving dysfunction in people with bipolar disorder.

Protocol

• Protocol: Kinase Assay ^[1]
• 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.
• Protocol: Animal Study ^[4]
• 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

References

• References: [1] Thomsen T, et al. Eur J Clin Chem Clin Biochem, 1991, 29(8), 487-492.
• References: [2] Pereira EF, et al. J Pharmacol Exp Ther, 1994, 270(2), 768-778.
• References: [3] Storch A, et al. Eur J Pharmacol, 1995, 290(3), 207-219.
• References: [4] Lorrio S, et al. J Pharmacol Exp Ther, 2007, 322(2), 591-599.

Sigma Aldrich - G1660

Biochem/physiol Actions
Cholinesterase inhibitor; reverses scopolamine-induced amnesia; antimyasthenic.

REFERENCES

• Thomsen T, et al. Eur J Clin Chem Clin Biochem, 1991, 29(8), 487-492.
• Pereira EF, et al. J Pharmacol Exp Ther, 1994, 270(2), 768-778.
• Storch A, et al. Eur J Pharmacol, 1995, 290(3), 207-219.
• Lorrio S, et al. J Pharmacol Exp Ther, 2007, 322(2), 591-599.