QuickView for Rivastigmine (compound)

Summary
General Info

PubChem

PubChem Compound 10586926

Name:	rivastigmine
PubChem Compound ID:	10586926
Molecular formula:	C₁₄H₂₂N₂O₂
Molecular weight:	252.345 g/mol

DrugBank

Identification

Name:	rivastigmine
Name (isomeric):	DB00989
Drug Type:	small molecule
Synonyms:	Ena 713 Free Base; Rivastigmine Hydrogen Tartrate
Brand:	Exelon Patch, Exelon
Category:	Parasympathomimetics, Nootropic Agents, Cholinesterase Inhibitors, Cholinergic Agents, Neuroprotective Agents
CAS number:	123441-03-2

Pharmacology

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... show more » 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. show less «
Mechanism of Action:	Rivastigmine is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine. The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hyd... show more » Rivastigmine is a carbamate derivative that is structurally related to physostigmine, but not to donepezil and tacrine. The precise mechanism of rivastigmine has not been fully determined, but it is suggested that rivastigmine binds reversibly with and inactivates chlolinesterase (eg. acetylcholinesterase, butyrylcholinesterase), preventing the hydrolysis of acetycholine, and thus leading to an increased concentration of acetylcholine at cholinergic synapses. The anticholinesterase activity of rivastigmine is relatively specific for brain acetylcholinesterase and butyrylcholinesterase compared with those in peripheral tissues. show less «
Protein binding:	40%
Biotransformation:	Rivastigmine is rapidly metabolized by cholinesterase-mediated hydrolysis.
Route of 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.
Half Life:	1.5 hours
Clearance:	renal cl=2.1-2.8 L/hr
Affected organisms:	Humans and other mammals

Interactions

Drug interaction:

Tizanidine	Possible antagonism of action
Oxybutynin	Possible antagonism of action
Chlorprothixene	Possible antagonism of action
Mesoridazine	Possible antagonism of action
Loxapine	Possible antagonism of action

Tizanidine	Possible antagonism of action
Oxybutynin	Possible antagonism of action
Chlorprothixene	Possible antagonism of action
Mesoridazine	Possible antagonism of action
Loxapine	Possible antagonism of action
Orphenadrine	Possible antagonism of action
Mirtazapine	Possible antagonism of action
Diphenhydramine	Possible antagonism of action
Benztropine	Possible antagonism of action
Clemastine	Possible antagonism of action
Biperiden	Possible antagonism of action
Desipramine	Possible antagonism of action
Azatadine	Possible antagonism of action
Chlorpheniramine	Possible antagonism of action
Amantadine	Possible antagonism of action
Thioproperazine	Possible antagonism of action
Promethazine	Possible antagonism of action
Maprotiline	Possible antagonism of action
Glutethimide	Possible antagonism of action
Nortriptyline	Possible antagonism of action
Cyclobenzaprine	Possible antagonism of action
Glycopyrrolate	Possible antagonism of action
Cyproheptadine	Possible antagonism of action
Cimetidine	Possible antagonism of action
Chlorpromazine	Possible antagonism of action
Doxepin	Possible antagonism of action
Procainamide	Possible antagonism of action
Propericiazine	Possible antagonism of action
Disopyramide	Possible antagonism of action
Meperidine	Possible antagonism of action
Thioridazine	Possible antagonism of action
Methotrimeprazine	Possible antagonism of action
Isocarboxazid	Possible antagonism of action
Imipramine	Possible antagonism of action
Amoxapine	Possible antagonism of action
Quetiapine	Possible antagonism of action
Trifluoperazine	Possible antagonism of action
Cyclizine	Possible antagonism of action
Amitriptyline	Possible antagonism of action
Moclobemide	Possible antagonism of action
Flavoxate	Possible antagonism of action
Trospium	The therapeutic effects of the anticholinergic, Trospium, and/or the acetylcholinesterase inhibitor (central), Rivastigmine, may be reduced due to antagonism. Monitor therapeutic effects of both agents.
Brompheniramine	Possible antagonism of action
Meclizine	Possible antagonism of action
Clomipramine	Possible antagonism of action
Pimozide	Possible antagonism of action
Flupenthixol	Possible antagonism of action
Prochlorperazine	Possible antagonism of action
Hyoscyamine	Possible antagonism of action
Dicyclomine	Possible antagonism of action
Darifenacin	Possible antagonism of action
Hydroxyzine	Possible antagonism of action
Trihexyphenidyl	Possible antagonism of action
Clozapine	Possible antagonism of action
Olanzapine	Possible antagonism of action
Trazodone	Possible antagonism of action
Perphenazine	Possible antagonism of action
Quinidine	Possible antagonism of action
Dimenhydrinate	Possible antagonism of action
Trimethobenzamide	The therapeutic effects of the anticholinergic, Trimethobenzamide, and/or the acetylcholinesterase inhibitor (central), Rivastigmine, may be reduced due to antagonism. Monitor therapeutic effects of both agents.
Phenelzine	Possible antagonism of action

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Targets

Acetylcholinesterase

Rapidly hydrolyzes choline released into the synapse

UniProt ID:

P22303

Gene:

ACHE

Actions:

inhibitor

References:

Kennedy JS, Polinsky RJ, Johnson B, Loosen P, Enz A, Laplanche R, Schmidt D, Mancione LC, Parris WC, Ebert MH: Preferential cerebrospinal fluid acetylcholinesterase inhibition by rivastigmine in humans. J Clin Psychopharmacol. 1999 Dec;19(6):513-21.
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Goldblum D, Garweg JG, Bohnke M: Topical rivastigmine, a selective acetylcholinesterase inhibitor, lowers intraocular pressure in rabbits. J Ocul Pharmacol Ther. 2000 Feb;16(1):29-35.
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Grossberg GT, Stahelin HB, Messina JC, Anand R, Veach J: Lack of adverse pharmacodynamic drug interactions with rivastigmine and twenty-two classes of medications. Int J Geriatr Psychiatry. 2000 Mar;15(3):242-7.
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Stahl SM: The new cholinesterase inhibitors for Alzheimer's disease, Part 1: their similarities are different. J Clin Psychiatry. 2000 Oct;61(10):710-1.
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Gottwald MD, Rozanski RI: Rivastigmine, a brain-region selective acetylcholinesterase inhibitor for treating Alzheimer's disease: review and current status. Expert Opin Investig Drugs. 1999 Oct;8(10):1673-1682.
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Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
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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.
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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.
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Lalli S, Albanese A: Rivastigmine in Parkinson's disease dementia. Expert Rev Neurother. 2008 Aug;8(8):1181-8.
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Onor ML, Trevisiol M, Aguglia E: Rivastigmine in the treatment of Alzheimer's disease: an update. Clin Interv Aging. 2007;2(1):17-32.
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Farlow MR: Update on rivastigmine. Neurologist. 2003 Sep;9(5):230-4.
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Greig NH, Lahiri DK, Sambamurti K: Butyrylcholinesterase: an important new target in Alzheimer's disease therapy. Int Psychogeriatr. 2002;14 Suppl 1:77-91.
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Cholinesterase

Enzymes

Cytochrome P450 2D6

Cytochrome P450 3A4