Ривастигмин

Использование

Antidepressant

Определение

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.

Общее описание

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.

Фармакокине?тика

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.

Метаболизм

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.