Rivastigmine

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Image:Rivastigmine.png
Rivastigmine
Systematic (IUPAC) name
2,6-dioxo-4-phenyl-piperidine-3-carbonitrile
Identifiers
CAS number	123441-03-2
ATC code	N06 DA03
PubChem	77991
DrugBank	APRD00321
Chemical data
Formula	C₁₄H₂₂N₂O₂
Mol. weight	250.337 g/mol
Pharmacokinetic data
Bioavailability	96%
Protein binding	40%
Metabolism	?
Half life	1.5 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Rivastigmine is a parasympathomimetic or cholinergic agent that was developed by Novartis for the treatment of mild to moderate dementia of the Alzheimer’s type and launched in the the European Union in 1998 and in the US in 2000. It is sold in the US under that trade name Exelon® but is also known as Prometax® in the UK. It was previously known as SDZ ENA 713. ^[1]

In 2006, it became the first product approved by the US FDA for the treatment of mild to moderate dementia associated with Parkinson's Disease. ^[2]

1 Pharmacology
2 Pharmacokinetics
3 Metabolism
4 Clinical Use
5 References
6 See also

[edit] Pharmacology

Rivastigmine tartrate is a white to off-white fine crystalline powder that is very soluble in water. The compound is a derivative of miotine and is considered a pseudo-irreversable cholinesterase inhibitor that also shows activity in inhibiting butylcholinesterase. ^[3] There is no evidence that rivastigmine alters the course of the underlying dementing process.

[edit] Pharmacokinetics

The compound is well absorbed with bioavailabilty about 40% in the 3mg dose. It is linear up to 3mg BID but non-linear at higher doses. Elimination is through the urine. Peak plasma concentrations are seen in about one hour, with peak CSF concentrations at 1.4-2.7 hours. The compound does cross the blood-brain barrier. Plasma protein binding is 40%. Because the compound has inhibition of acetylcholinesterase (AChE) of up to 10 hours, it is sometime called an “intermediate acting agent” as compared to donepezil which is short-acting.

[edit] Metabolism

The major route of metabolism for rivastigmine is via cholinesterase-mediated hydrolysis into ZNS 114-666 at the site of the action in the CNS. Elimination bypasses the hepatic system and passes out through the renal system. Hepatic cytochrome P450 (CYP) isoenzymes are not in the pathway for this compound. ^[4]

Rivastigmine shows some preference over other AChE inhibitors in its inhibition in the neocortex and hippocampus as compared to other organ systems.

[edit] Clinical Use

Rivastigmine is approved for mild to moderate dementia of the Alzheimer’s type and for mild to moderate dementia related to Parkinson's disease.

[edit] References

^ Novartis Pharmaceuticals Corporation “Exelon Product Insert” June 2006. [1]
^ “FDA Approves the First Treatment for Dementia of Parkinson’s Disease” US FDA News Release [2]
^ Camps P. Munoz-Torrero D. “Cholinergic drugs in pharmacotherapy of Alzheimer's disease.” Mini Rev Med Chem. 2002 Feb;2(1):11-25. PMID 12369954
^ Jann MW. “Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease.” Pharmacotherapy. Jan 2000 20(1):1-12. PMID 10641971