Rivastigmine

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Rivastigmine, also known as Exelon

Better Known as: Exelon

  • Marketed By: Novartis
  • Major Indication: Alzheimer's Disease
  • Drug Class: Acetylcholinesterase Inhibitor
  • Date of FDA Approval (Patent Expiration): 2007 (
  • 2006 Sales: $220 Million[1]
  • Importance: One of the the first treatments for the symptoms of Alzheimer's Disease, although no definitive proof exists as to whether it alters the progression of the disease.
  • See: Pharmaceutical Drugs for more information about other drugs and disorders

Mechanism of Action

Rivastigmine is an Acetylcholinesterase (AChE) inhibitor. It binds to the active site of , utilizing many of the same residues which bind and break down acetylcholine. By inhibiting AChE, the important neurotransmitter, acetylcholine, is degraded at a slower rate, helping reverse the marked decrease in neuronal function evident in Alzheimer's Disease patients. Rivastigmine is rapidly metabolized into its principal components (carbamyl and NAP moieties) which are powerful Acetylcholine inhibitors. These components primarily GLy 117, Gly 118, Gly 119 Ala 201, Trp 233, Phe 290, Trp 84, Phe 330, His 440, & Phe 288 in tightly binding to the AChE binding site via pi stacking and hydrogen bond interactions. Rivastigmine outcompetes acetylcholine for the active site of AChE, inhibiting the esterase.[2]

Pharmacokinetics

Acetylcholinesterase Inhibitor Pharmacokinetics
Parameter Donepezil Tacrine Rivastigmine Galantamine
Tmax (hr) 3.6 1.5 .3 1.2
Cmax (ng/ml) 6.5 15.7 29.3 42.6
Bioavailability (%) 100 17 36 100
Protein Binding (%) 96 55 40 10
T1/2 (hr) 70 3 5 7.3
AUC (ng/ml/hr) 380 80.4 191 427
IC50 (nM) 6.7
(Rat)
450
(Human)
1535
(Human)
1995
(Rat)
Dosage (mg) 5 160 6 8
Metabolism Hepatic (CYP2D6 & CYP3A4) & AChE Hepatic (CYP1A2) & AChE AChE Hepatic (CYP3A4 & CYP2D6) & AChE

For Pharmacokinetic Data References, see: References

References

  1. Irena Melnikova, Therapies for Alzheimer's disease, Nature Reviews Drug Discovery 6, 341-342 (May 2007)
  2. Bar-On P, Millard CB, Harel M, Dvir H, Enz A, Sussman JL, Silman I. Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine. Biochemistry. 2002 Mar 19;41(11):3555-64. PMID:11888271


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