Rivastigmine, a New‐Generation Cholinesterase Inhibitor for the Treatment of Alzheimer's Disease

@article{Jann2000RivastigmineAN,
  title={Rivastigmine, a New‐Generation Cholinesterase Inhibitor for the Treatment of Alzheimer's Disease},
  author={Michael W. Jann},
  journal={Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy},
  year={2000},
  volume={20}
}
  • M. Jann
  • Published 1 January 2000
  • Medicine
  • Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
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… 
Review of rivastigmine and its clinical applications in Alzheimer’s disease and related disorders
TLDR
The consistent efficacy in treating all three domains (cognition, daily functioning and behaviour) and good tolerability, particularly with slow titration, makes rivastigmine a good first-line ChEI therapy for the treatment of AD.
An update on the safety of current therapies for Alzheimer’s disease: focus on rivastigmine
TLDR
Donepezil, rivastigmine and galantamine are the three ChEIs FDA-approved as first-line treatment for AD and the goal for the future would be to optimize the patch formulation to increase both efficacy and safety.
Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase - Design, synthesis and biological evaluation
TLDR
Several promising MTDLs derived from tacrine exhibited in vivo efficacy in rats by protecting against behavioral impairment induced by administration of the excitotoxic agent, monosodium glutamate, and several of these synthesized compounds exhibited promising inhibitory activities against butyrylcholinesterase and β-secretase.
Donepezil and Rivastigmine: Pharmacokinetic Profile and Brain-targeting After Intramuscular Administration in Rats
TLDR
Both compounds showed ability to target the central nervous system, with brain concentrations exceeding those in plasma, and differences in brain profile can be most easily expressed by plasma/brain AUCtotal ratios.
Clinical Pharmacokinetics and Pharmacodynamics of Cholinesterase Inhibitors
TLDR
The knowledge base for the pharmacokinetics and pharmacodynamics of cholinesterase inhibitors continues to expand and increased information available to clinicians can optimise the use of these agents in the management of patients with Alzheimer’s disease.
Velnacrine thiaanalogues as potential agents for treating Alzheimer's disease.
TLDR
This work modified the cyclohexyl ring of velnacrine, a less toxic analogue of tacrine, by synthesizing a series of thiopyranoquinolines in which the C-3 methylene unit was replaced by a sulphur atom.
Rivastigmine Transdermal Patch
TLDR
Treatment with the rivastigmine 9.5 mg/ 24 hours patch was generally well tolerated by patients with Alzheimer’s disease and significantly more caregivers of study patients preferred administering the patch formulation of rivASTigmine than the capsule formulation.
Rivastigmine transdermal patch: role in the management of Alzheimer's disease.
  • D. Guay
  • Medicine
    The Consultant pharmacist : the journal of the American Society of Consultant Pharmacists
  • 2008
TLDR
The TD formulation significantly reduces GI intolerance as compared with oral doses producing the same degree of systemic exposure, as a result of the lower peak plasma concentration, lower degree of peak-trough concentration fluctuation, and prolonged time to peak concentration achieved with the TD formulation.
Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE.
TLDR
A molecular modelling study was performed to explore the ability of this inhibitor to bind simultaneously to both sites of the enzyme and make it a promising lead for developing disease-modifying drugs for the future treatment of Alzheimer's disease.
Rivastigmine: an update on therapeutic efficacy in Alzheimer's disease and other conditions
  • C. Gabelli
  • Medicine
    Current medical research and opinion
  • 2003
SUMMARY The results of recent clinical trials with rivastigmine show that in the approved indication of mild to moderate Alzheimer's disease (AD), the drug is effective in the long term. Rivastigmine
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 61 REFERENCES
Clinical pharmacology of rivastigmine: a new-generation acetylcholinesterase inhibitor for the treatment of Alzheimer's disease.
TLDR
Consistent with rivastigmine's pharmacokinetic and pharmacodynamic profiles, Phase II and III trials have demonstrated that the drug is a well-tolerated and effective treatment for AD.
Rivastigmine. A review of its use in Alzheimer's disease.
TLDR
Rivastigmine is a useful option for the treatment of patients with mild to moderately severe Alzheimer's disease and, given the lack of established treatment options, it should be considered for first-line use in this population.
EFFICACY AND TOLERABILITY OF RIVASTIGMINE IN PATIENTS WITH DEMENTIA OF THE ALZHEIMER TYPE
TLDR
Rivastigmine appears to be effective in the treatment of patients with probable Alzheimer's disease and is well tolerated at a dosage of 6 mg/d, and the low incidence of adverse events and good tolerability seen in this study suggest that higher daily doses of rivastIGmine could be used in future trials, possibly leading to enhanced efficacy.
Effects of Novel Cholinesterase Inhibitors Based on the Mechanism of Enzyme Inhibition
TLDR
The failure of physostigmine to induce improvements in many of the patients reported in the literature may be due to failure to achieve adequate CNS AChE inhibition, as well as intrinsic liver toxicity, although the elevation of liver enzyme activity is reversible following withdrawal of the drug.
Pharmacological evaluation of phenyl-carbamates as CNS-selective acetylcholinesterase inhibitors.
TLDR
SDZ ENA 713 produced a 10-fold greater inhibition of AChE in the hippocampus and cortex than in the heart and skeletal muscle, which explains its relatively low toxicity and freedom from cholinergic side effects.
Pharmacologic and Clinicopharmacologic Properties of SDZ ENA 713, a Centrally Selective Acetylcholinesterase Inhibitor
TLDR
Some pharmacologic properties of a novel AChEI, SDZ ENA 713, that readily penetrates the central nervous system after parenteral and oral administration are described and appear to have greater chemical stability and longer duration of action than does physostigmine.
Dose‐dependent CSF acetylcholinesterase inhibition by SDZ ENA 713 in Alzheimer's disease
TLDR
Rapid, sustained, dose‐dependent inhibition of CSF AChE suggests that SDZ ENA 713 has therapeutic potential in AD patients.
Cholinesterase Inhibitors: A Therapeutic Strategy for Alzheimer Disease
TLDR
Compared to placebo, new AChEIs in development provide modest improvements in cognition for patients with mild to moderate AD, with improved tolerability profiles and more convenient dosing relative to tacrine.
Cholinesterase Inhibitors in the Treatment of Alzheimer’s Disease
TLDR
Tacrine is associated with hepatotoxicity while other cholinesterase inhibitors seem devoid this adverse effect, and concomitant medication with various drugs with rivastigmine does not seem to cause any drug interactions in patients with Alzheimer’s disease.
Guidelines for the Appropriate Use of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease
TLDR
These guidelines will provide the starting point for a wider clinical use because, although available and clinically effective, the cholinesterase inhibitors are under-prescribed by clinicians in the pharmacological treatment of Alzheimer’s disease.
...
1
2
3
4
5
...