3-[(1S)-1-(dimethylamino)ethyl]phenyl N-ethyl-N-methylcarbamate

• ChemBase ID: 863
• Molecular Formular: C14H22N2O2
• Molecular Mass: 250.33668
• Monoisotopic Mass: 250.16812795
• SMILES: O(c1cc([C@@H](N(C)C)C)ccc1)C(=O)N(CC)C
• Canonical SMILES: CCN(C(=O)Oc1cccc(c1)[C@@H](N(C)C)C)C
• InChI: InChI=1S/C14H22N2O2/c1-6-16(5)14(17)18-13-9-7-8-12(10-13)11(2)15(3)4/h7-11H,6H2,1-5H3/t11-/m0/s1
• InChIKey: XSVMFMHYUFZWBK-NSHDSACASA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-[(1S)-1-(dimethylamino)ethyl]phenyl N-ethyl-N-methylcarbamate
• IUPAC Traditional name: rivastigmine; exelon
• Brand Name: Exelon; Exelon Patch
• Synonyms: Ena 713 Free Base; Rivastigmine Hydrogen Tartrate; rivastigmine; Rivastigmine; Rivastigmine tartrate

Database IDs

• CAS Number: 123441-03-2; 129101-54-8
• PubChem SID: 46507452; 160964326
• PubChem CID: 77991

CALCULATED PROPERTIES

JChem

• H Acceptors: 2
• H Donor: 0
• LogD (pH = 5.5): -0.7295023
• LogD (pH = 7.4): 0.9140339
• Log P: 2.4090931
• Molar Refractivity: 73.3706 cm^3
• Polarizability: 28.459797 Å^3
• Polar Surface Area: 32.78 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.45
• LOG S: -2.09
• Solubility (Water): 2.04e+00 g/l

PROPERTIES

Physical Property

• Hydrophobicity(logP): 2.3

Product Information

• Purity: 98%

DETAILS

DrugBank - DB00989

• Drug Groups: approved; investigational
• Description: Rivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer's type. Rivastigmine is a cholinesterase inhibitor that inhibits both butyrylcholinesterase and acetylcholinesterase.
• Indication: For the treatment of mild to moderate dementia associated with Parkinson's disease or of the Alzheimer's type.
• Pharmacology: Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. 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. While the precise mechanism of rivastigmine's action is unknown, it 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 cholinesterase. If this proposed mechanism is correct, rivastigmine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact.
• Affected Organisms: Humans and other mammals
• Biotransformation: Rivastigmine is rapidly metabolized by cholinesterase-mediated hydrolysis.
• Half Life: 1.5 hours
• Protein Binding: 40%
• Elimination: Rivastigmine is extensively metabolized primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite NAP226-90. Renal excretion of the metabolites is the major route of elimination. Less than 1% of the administered dose is excreted in the feces.
• Distribution: * 1.8 to 2.7 L/kg
• Clearance: * renal cl=2.1-2.8 L/hr
• References: Camps P, Munoz-Torrero D: Cholinergic drugs in pharmacotherapy of Alzheimer's disease. Mini Rev Med Chem. 2002 Feb;2(1):11-25. [Pubmed] ; Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M: Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. BMJ. 1999 Mar 6;318(7184):633-8. [Pubmed] ; Finkel SI: Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer's disease. Clin Ther. 2004 Jul;26(7):980-90. [Pubmed] ; Rosler M, Retz W, Retz-Junginger P, Dennler HJ: Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease. Behav Neurol. 1998;11(4):211-216. [Pubmed] ; Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R: Rivastigmine for dementia associated with Parkinson's disease. N Engl J Med. 2004 Dec 9;351(24):2509-18. [Pubmed] ; Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE: Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001191. [Pubmed] ; Naik RS, Hartmann J, Kiewert C, Duysen EG, Lockridge O, Klein J: Effects of rivastigmine and donepezil on brain acetylcholine levels in acetylcholinesterase-deficient mice. J Pharm Pharm Sci. 2009;12(1):79-85. [Pubmed] ; Farlow MR: Update on rivastigmine. Neurologist. 2003 Sep;9(5):230-4. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Camps P, Munoz-Torrero D: Cholinergic drugs in pharmacotherapy of Alzheimer's disease. Mini Rev Med Chem. 2002 Feb;2(1):11-25. Pubmed
• Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M: Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial. BMJ. 1999 Mar 6;318(7184):633-8. Pubmed
• Finkel SI: Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer's disease. Clin Ther. 2004 Jul;26(7):980-90. Pubmed
• Rosler M, Retz W, Retz-Junginger P, Dennler HJ: Effects of two-year treatment with the cholinesterase inhibitor rivastigmine on behavioural symptoms in Alzheimer's disease. Behav Neurol. 1998;11(4):211-216. Pubmed
• Emre M, Aarsland D, Albanese A, Byrne EJ, Deuschl G, De Deyn PP, Durif F, Kulisevsky J, van Laar T, Lees A, Poewe W, Robillard A, Rosa MM, Wolters E, Quarg P, Tekin S, Lane R: Rivastigmine for dementia associated with Parkinson's disease. N Engl J Med. 2004 Dec 9;351(24):2509-18. Pubmed
• Farlow MR: Update on rivastigmine. Neurologist. 2003 Sep;9(5):230-4. Pubmed
• Birks J, Grimley Evans J, Iakovidou V, Tsolaki M, Holt FE: Rivastigmine for Alzheimer's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001191. Pubmed
• Naik RS, Hartmann J, Kiewert C, Duysen EG, Lockridge O, Klein J: Effects of rivastigmine and donepezil on brain acetylcholine levels in acetylcholinesterase-deficient mice. J Pharm Pharm Sci. 2009;12(1):79-85. Pubmed