Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease

Pharmacotherapy. 2000 Jan;20(1):1-12. doi: 10.1592/phco.20.1.1.34664.

Abstract

Rivastigmine is a cholinesterase inhibitor (ChEI) with a structural formula different from that of currently available ChEIs. Tacrine and donepezil are classified as short-acting or reversible agents since binding to acetylcholinesterase enzyme (AChE) is hydrolyzed within minutes. Rivastigmine is classified as an intermediate-acting or pseudo-irreversible agent due to its long inhibition on AChE of up to 10 hours. Preclinical biochemical studies indicated that rivastigmine has central nervous system selectivity over peripheral inhibition. It ameliorated memory impairment in rats with forebrain lesions. The drug is rapidly absorbed orally, with a bioavailability of 0.355 and low protein binding (40%). Its elimination half-life is less than 2 hours, and it is converted to an inactive metabolite at the site of action, bypassing hepatic metabolic pathways. Its disposition essentially is unaltered in patients with renal or hepatic impairment. It also has dose-dependent effects on AChE inhibition. In the two large multicenter clinical trials (total 1324 patients) that used a forced-dosage titration scheme, rivastigmine 6-12 mg/day was superior to placebo on three cognitive and functioning scales (p<0.001). Gastrointestinal symptoms are the most frequently reported adverse events. They occurred mostly during the dosage titration phase and decreased during the maintenance phase. Rivastigmine offers clinicians another therapeutic agent to treat Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Animals
  • Carbamates / adverse effects
  • Carbamates / chemistry
  • Carbamates / therapeutic use*
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Multicenter Studies as Topic
  • Neuroprotective Agents / adverse effects
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / therapeutic use*
  • Phenylcarbamates*
  • Rats
  • Rivastigmine

Substances

  • Carbamates
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Phenylcarbamates
  • Rivastigmine