1,2,3,4-tetrahydroacridin-9-amine

• ChemBase ID: 266
• Molecular Formular: C13H14N2
• Molecular Mass: 198.26366
• Monoisotopic Mass: 198.11569846
• SMILES: n1c2c(CCCC2)c(N)c2c1cccc2
• Canonical SMILES: Nc1c2CCCCc2nc2c1cccc2
• InChI: InChI=1S/C13H14N2/c14-13-9-5-1-3-7-11(9)15-12-8-4-2-6-10(12)13/h1,3,5,7H,2,4,6,8H2,(H2,14,15)
• InChIKey: YLJREFDVOIBQDA-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1,2,3,4-tetrahydroacridin-9-amine
• IUPAC Traditional name: tacrine
• Brand Name: Cognex; Romotal
• Synonyms: 1,2,3,4-Tetrahydroacridin-9-amine; 9-AMINOTETRAHYDROACRIDINE; Tetrahydroaminacrine; Tetrahydroaminoacridine; Tetrahydroaminocrin; Tetrahydroaminocrine; THA; Tacrine

Database IDs

• CAS Number: 321-64-2; 7149-50-0
• EC Number: 206-291-2
• MDL Number: MFCD00046923
• PubChem SID: 160963729; 46505487
• PubChem CID: 1935

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 0.83008754
• LogD (pH = 7.4): 1.254769
• Log P: 2.6281447
• Molar Refractivity: 61.7381 cm^3
• Polarizability: 24.629675 Å^3
• Polar Surface Area: 38.91 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.13
• LOG S: -3.16
• Solubility (Water): 1.36e-01 g/l

PROPERTIES

Physical Property

• Solubility: 217 mg/L
• Melting Point: 284°C
• Hydrophobicity(logP): 2.2

Safety Information

• Storage Warning: IRRITANT
• RTECS: AR9532100
• European Hazard Symbols: Toxic (T)
• Risk Statements: R:25
• Safety Statements: S:28-29-36/37/39-45

Product Information

• Purity: 95+%

DETAILS

DrugBank - DB00382

• Drug Groups: approved
• Description: A centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. [PubChem]
• Indication: For the palliative treatment of mild to moderate dementia of the Alzheimer's type.
• Pharmacology: Tacrine is a parasympathomimetic- a reversible cholinesterase inhibitor that 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. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine at cholinergic synapses through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, tacrine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that tacrine alters the course of the underlying dementing process.
• Toxicity: Overdosage with cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. The estimated median lethal dose of tacrine following a single oral dose in rats is 40 mg/kg, or approximately 12 times the maximum recommended human dose of 160 mg/day.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Cytochrome P450 1A2 is the principal isozyme involved in tacrine metabolism. The major metabolite, 1-hydroxy-tacrine (velnacrine), has central cholinergic activity.
• Absorption: Tacrine is rapidly absorbed. Absolute bioavailability of tacrine is approximately 17%.
• Half Life: 2 to 4 hours
• Protein Binding: 55%
• Distribution: * 349 ± 193 L
• References: Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M: Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration. JAMA. 1998 Nov 25;280(20):1777-82. [Pubmed] ; Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: Pubmed
• Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M: Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration. JAMA. 1998 Nov 25;280(20):1777-82. Pubmed