(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

• ChemBase ID: 556
• Molecular Formular: C17H21NO3
• Molecular Mass: 287.35354
• Monoisotopic Mass: 287.15214354
• SMILES: O1[C@@H]2[C@]3(c4c1c(OC)ccc4CN(CC3)C)C=C[C@H](O)C2
• Canonical SMILES: COc1ccc2c3c1O[C@@H]1[C@@]3(CCN(C2)C)C=C[C@@H](C1)O
• InChI: InChI=1S/C17H21NO3/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/t12-,14-,17-/m0/s1
• InChIKey: ASUTZQLVASHGKV-JDFRZJQESA-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
• IUPAC Traditional name: galantamine
• Brand Name: Galantamin; Jilkon; Lycoremin; Lycoremine; Reminyl
• Synonyms: Galanthamine; Galanthamine hydrobromide; (-)-Galanthamine; Galantamine

Database IDs

• CAS Number: 357-70-0
• PubChem SID: 160964019; 46505659
• PubChem CID: 9651; 908828

CALCULATED PROPERTIES

JChem

• 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

ALOGPS 2.1

• Log P: 1.39
• LOG S: -2.23
• Solubility (Water): 1.70e+00 g/l

PROPERTIES

Physical Property

• Solubility: 10 mg/mL (HBr salt)
• Hydrophobicity(logP): 1.8

DETAILS

DrugBank - DB00674

• Drug Groups: approved
• Description: A benzazepine derived from norbelladine. It is found in galanthus and other amaryllidaceae. Galantamine is a cholinesterase inhibitor that has been used to reverse the muscular effects of gallamine triethiodide and tubocurarine, and has been studied as a treatment for Alzheimer's disease and other central nervous system disorders. [PubChem]
• Indication: For the treatment of mild to moderate dementia of the Alzheimer's type. Has also been investigated in patients with mild cognitive impairment who did not meet the diagnostic criteria for Alzheimer's disease.
• Pharmacology: Galantamine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. It is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Galantamine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, Galantamine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that Galantamine alters the course of the underlying dementing process.
• Toxicity: LD₅₀=75 mg/kg (rat)
• Affected Organisms: Humans and other mammals
• Half Life: 7 hours
• Protein Binding: 18%
• Elimination: Galantamine is metabolized by hepatic cytochrome P450 enzymes, glucuronidated, and excreted unchanged in the urine.
• Distribution: * 175 L
• Clearance: * 300 mL/min [After IV. or oral administration]
• References: Scott LJ, Goa KL: Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000 Nov;60(5):1095-122. [Pubmed] ; Greenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL: Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution. FEBS Lett. 1999 Dec 17;463(3):321-6. [Pubmed] ; Woodruff-Pak DS, Vogel RW 3rd, Wenk GL: Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2089-94. Epub 2001 Feb 6. [Pubmed] ; Birks J: Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. [Pubmed] ; Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. [Pubmed] ; Olin J, Schneider L: Galantamine for Alzheimer's disease. Cochrane Database Syst Rev. 2002;(3):CD001747. [Pubmed] ; Scott LJ, Goa KL: Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000 Nov;60(5):1095-122. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Scott LJ, Goa KL: Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000 Nov;60(5):1095-122. Pubmed
• Greenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL: Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution. FEBS Lett. 1999 Dec 17;463(3):321-6. Pubmed
• Woodruff-Pak DS, Vogel RW 3rd, Wenk GL: Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2089-94. Epub 2001 Feb 6. Pubmed
• Birks J: Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. Pubmed
• Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. Pubmed
• Olin J, Schneider L: Galantamine for Alzheimer's disease. Cochrane Database Syst Rev. 2002;(3):CD001747. Pubmed
• Scott LJ, Goa KL: Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000 Nov;60(5):1095-122. Pubmed