Rivastigmine
Systematic (IUPAC) name
(S)-N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate hydrogen-(2R,3R)-tartrate
Identifiers
CAS number	123441-03-2
ATC code	N06DA03
PubChem	77991
DrugBank	APRD00321
Chemical data
Formula	C14H22N2O2
Mol. mass	250. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System containing Psychoanaleptics. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 337 g/mol
Pharmacokinetic data
Bioavailability	96%
Protein binding	40%
Metabolism	Hepatic, via pseudocholinesterase
Half life	1. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals In Biochemistry, cholinesterase is an enzyme that catalyzes the Hydrolysis of the Neurotransmitter Acetylcholine into The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 5 hours
Excretion	Renal, 97%
Therapeutic considerations
Pregnancy cat.	B(US)
Legal status	℞-only(US)
Routes	Oral, Transdermal

Rivastigmine (sold under the trade name Exelon) is a parasympathomimetic or cholinergic agent that was developed by Novartis for the treatment of mild to moderate dementia of the Alzheimer’s type. Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route A parasympathomimetic drug is a drug or Poison that acts by stimulating or mimicking the Parasympathetic nervous system (PSNS A receptor is cholinergic if it uses Acetylcholine as its Neurotransmitter. Novartis International AG is a multinational Pharmaceutical company based in Basel Switzerland that manufactures drugs such as Clozapine Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. In 2006, it became the first product approved globally for the treatment of mild to moderate dementia associated with Parkinson's Disease. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's ^[1] Rivastigmine has been available in capsule and liquid formulations since 1997. ^[2] In 2007 the rivastigmine transdermal patch became the first patch treatment for dementia.

Rivastigmine tartrate is a white to off-white fine crystalline powder that is both lipophilic (soluble in fats) and hydrophilic (soluble in water). A tartrate is a Salt or Ester of the Organic compound Tartaric acid, a Dicarboxylic acid. Rivastigmine is a cholinesterase inhibitor that inhibits both butyrylcholinesterase and acetylcholinesterase (unlike donepezil which is selective for acetylcholinesterase). An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine Butyrylcholinesterase, also known as BCHE, is a human Gene. Butyrylcholinesterase is also called serum cholinesterase Donepezil (also used incorrectly as Donezepil marketed under the trade name Aricept ( Eisai) ( Pfizer) is a centrally acting reversible Acetylcholinesterase It is thought that rivastigmine works by inhibiting these cholinesterase enzymes, which would otherwise break down the brain chemical acetylcholine. ^[3] Its efficacy is similar to donepezil and tacrine. Tacrine is a Parasympathomimetic and a centrally acting Cholinesterase inhibitor (anticholinesterase Doses below 6mg/d may be ineffective. The effects of this kind of drugs in different kinds of dementia (including Alzheimer's dementia) are modest, and it is still unclear which AcCh(ButCh) esterase inhibitor is better in Parkinson's dementia, though rivastigmine is well-studied. We still do not have enough postmarketing clinical experience with rivastigmine patch, but initial reports are encouraging.

Contents 1 Clinical use 2 Pharmacokinetics 3 References 4 See also

Clinical use

The FDA has approved rivastigmine capsules and rivastigmine patch for the treatment of mild to moderate dementia of the Alzheimer’s type and for mild to moderate dementia related to Parkinson's disease. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's It has been used in more than 6 million patients world-wide.

Rivastigmine has demonstrated significant treatment effects on the cognitive (thinking and memory), functional (activities of daily living) and behavioural problems that are commonly associated with Alzheimer’s^[4][5][6][7] and Parkinson's disease dementias. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's ^[8]

In patients with either type of dementia, rivastigmine has been shown to provide meaningful symptomatic effects that may allow patients to remain independent and ‘be themselves’ for longer. In particular, rivastigmine appears to show marked treatment effects in patients showing a more course of aggressive disease, such as those with a younger age of onset, a poor nutritional status, or those experiencing symptoms such as delusions or hallucinations. ^[9] For example, the presence of hallucinations appears to be a predictor of especially strong responses to rivastigmine, both in Alzheimer’s and Parkinson's disease patients. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's ^[10][11] It has been proposed that these effects might reflect the additional inhibition of butyrylcholinesterase, which is implicated in symptom progression and might provide added benefits over acetylcholinesterase-selective drugs in some patients. ^[12][13] Multi-infarct dementia - may be slight improvement in executive functions and behaviour. The usage in schizophrenia patients - there are no firm evidences.

On the other hand, it has been postulated that the strong potency of rivastigmine, provided by its dual inhibitory mechanism, leads to more nausea and vomiting during the titration phase of oral rivastigmine treatment (all cholinesterase inhibitors require doses to be increased gradually over several weeks, and this is usually referred to as the ‘titration phase’). ^[14] This enforces the importance of taking oral forms of these drugs as prescribed with food. ^[15] However, rates of nausea and vomiting are markedly reduced with the once-daily rivastigmine patch (which can be applied at any time of the day, with or without food).

In a large clinical trial of the rivastigmine patch in 1,195 patients with Alzheimer’s disease, the target dose of 9. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. 5 mg/24 hour patch provided similar clinical effects (e. g. memory and thinking, activities of daily living, concentration) as the highest doses of rivastigmine capsules, but with three times fewer reports of nausea and vomiting. ^[16].

Oral doses of rivastigmine should be titrated, with a 3mg per day step every 2 to 4 weeks. Rivastigmine is classified as Pregnancy category B, with insufficient data on risks associated with breastfeeding. The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during In cases of overdose, atropine was used to reverse bradycardia. Atropine is a Tropane Alkaloid extracted from Deadly nightshade ( Atropa belladonna) Jimsonweed (Datura stramonium and other plants Bradycardia, as applied to adult medicine is defined as a resting Heart rate of under 60 beats per minute though it is seldom symptomatic until the rate drops below 50 beat/min Dialysis is ineffective due to the half-life of the drug. In Medicine, dialysis (from Greek "dialusis" meaning dissolution "dia" meaning through and "lusis" meaning loosening is primarily

Pharmacokinetics

When given orally, rivastigmine is well absorbed with a bioavailability of about 40% in the 3 mg dose. Pharmacokinetics are linear up to 3 mg 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. 4-3. 8 hours. When given by once-daily transdermal patch, the pharmacokinetic profile of rivastigmine is much smoother, compared with capsules, with lower peak plasma concentrations and reduced fluctuations. ^[17] The 9. 5 mg/24 h rivastigmine patch provides comparable exposure to 12 mg/day capsules (the highest recommended oral dose). ^[18]

The compound does cross the blood-brain barrier. Plasma protein binding is 40%. ^[19] The major route of metabolism for rivastigmine is by its target enzymes via cholinesterase-mediated hydrolysis. Elimination bypasses the hepatic system so hepatic cytochrome P450 (CYP) isoenzymes are not involved. ^[20] It has been suggested that this means there is a low potential for drug-drug interactions (which could lead to adverse effects) between rivastigmine and the many common drugs that use the cytochrome P450 metabolic pathway. ^[21]

References

See also

• "Cholinesterase inhibitors" section of the "Cholinesterase" article

In Biochemistry, cholinesterase is an enzyme that catalyzes the Hydrolysis of the Neurotransmitter Acetylcholine into

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