Rivastigmine

The Uses of Rivastigmine

Antidepressant

Background

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.

Indications

For the treatment of mild to moderate dementia associated with Parkinson's disease or of the Alzheimer's type.

What are the applications of Application

(S)-Rivastigmine is an isomer of Rivastigimine, an acterylcholinesterase inhibitor

Definition

ChEBI: A carbamate ester obtained by formal condensation of the carboxy group of ethyl(methyl)carbamic acid with the phenolic OH group of 3-[(1S)-1-(dimethylamino)ethyl]phenol. A reversible cholinesterase inhibitor.

brand name

Exelon (Novartis).

General Description

Rivastigmine (Exelon, EA 713) is apseudoirreversible noncompetitive carbamate inhibitor ofAChE. Although the half-life is approximately 2 hours,the inhibitory properties of this agent last for 10 hours becauseof the slow dissociation of the drug from the enzyme.The Food and Drug Administration (FDA) approved its usein mild-to-moderate Alzheimer disease in April 2000. InJuly 2007, rivastigmine was granted approval for use inmanaging mild-to-moderate dementia associated withParkinson disease.

Pharmacokinetics

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.

Pharmacokinetics

Rivastigmine is a centrally selective, arylcarbamate AChEI that was approved in 2000 for oral administration in the treatment of AD. It has an elimination half-life of 1.4 to 1.7 hours but is able to inhibit AChE for up to 10 hours. Because of the slow dissociation of the carbamylated enzyme, it has been referred to as a pseudo-irreversible AChEI. Like donepezil, rivastigmine exhibits a low level of hepatotoxicity. It is rapidly and extensively hydrolyzed in the CNS by cholinesterase with minimal involvement of CYP450. The phenolic metabolite is excreted primarily via the kidneys.

Clinical Use

Mild-moderate dementia in Alzheimer’s disease
Idiopathic Parkinson’s disease

Drug interactions

Potentially hazardous interactions with other drugs
Muscle relaxants: enhances effect of suxamethonium; antagonises effect of non-depolarising muscle relaxants.

Metabolism

Rivastigmine is rapidly metabolized by cholinesterase-mediated hydrolysis.

Metabolism

Rivastigmine is the tertiary amines that are rapidly absorbed from the gastrointestinal tract, as are tacrine, donepezil, and galanthamine, whereas quaternary ammonium compounds are poorly absorbed after oral administration. Nevertheless, quaternary ammonium compounds like neostigmine and pyridostigmine are orally active if larger doses are employed. Only the quaternary ammonium inhibitors do not readily enter the CNS. Because of their high lipid solubility and low molecular weight, most of the organophosphates are absorbed by all routes of administration; even percutaneous exposure can result in the absorption of sufficient drug to permit the accumulation of toxic levels of these compounds.