Drug Reference for FDA Approved Alzheimer's Disease Drugs @ Neurotransmitter.net


Advertisement



Generic Name:
donepezil hydrochloride

Trade Name:
Aricept ® [Eisai (also marketed by Pfizer)]

IUPAC Name:
2-[(1-benzyl-4-piperidyl)
methyl]-5,6-dimethoxy-2,3-
dihydroinden-1-one hydrochloride

Dosage Forms/Routes:
Tablet/oral;
Solution/oral;
Tablet (orally disintegrating)/oral

Major Metabolites:
6-O-desmethyl donepezil;
donepezil-cis-N-oxide;
5-O-desmethyl donepezil;
5-O-desmethyl donepezil glucuronide

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
11/25/1996


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[
Link]

Epocrates:
[Link]

Empirical Formula:
C24H30ClNO3

Molecular Mass:
415.953 g/mol

Indications:
Treatment of mild to moderate dementia of the Alzheimer's type

Possible Mechanisms of Action:
Donepezil is a selective and reversible acetylcholinesterase inhibitor (1). Donepezil is a mixed type inhibitor of acetycholinesterase, meaning that it exhibits both noncompetitive and competitive components of inhibition (1).

Chemical Class:
benzylpiperidine derivative

PubChem 2D Structure:

"3D" Structure (Requires Chime):
[
Link] 

Generic Name:
galantamine hydrobromide

Trade Name:
Razadyne ® [Janssen]

Common Chemical Name:
(4aS,6R,8aS)-4a,5,9,10,11,12-
hexahydro-3-methoxy-11-
methyl-6H-benzofuro
[3a,3,2-ef][2]benzazepin-6-ol
hydrobromide

Major Metabolites:
O-desmethylgalantamine glucuronide
;
N-desmethylgalantamine;
epigalantamine

Dosage Forms/Routes:
Tablet/oral;
Solution/oral;
Capsule (extended release)/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
02/28/2001


Manufacturers:

[FDA Search]

Product Insert:
[Link]

[Link] (ER)

RxList:
[
Link]

Epocrates:
[Link]

Empirical Formula:
C17H22BrNO3

Molecular Mass:
368.266 g/mol

Indications:
Treatment of mild to moderate dementia of the Alzheimer's type

Possible Mechanisms of Action:
Galantamine is a competitive and reversible inhibitor of acetylcholinesterase (2). The drug also acts as a positive allosteric modulator at nicotinic acetylcholine receptors including the alpha4beta2 subtype (3).

Chemical Class:
phenanthrene alkaloid

PubChem 2D Structure:

Generic Name:
memantine hydrochloride

Trade Name:
Namenda ® [Forest Labs]

IUPAC Name:
3,5-dimethyladamantan-1-
amine hydrochloride

Major Metabolites:
N-gludantan conjugate of memantine;
6-hydroxymemantine;
1-nitroso-deaminated memantine

Dosage Forms/Routes:
Tablet/oral;
Solution/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
10/16/2003


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[
Link]

Epocrates:
[Link]

Empirical Formula:
C12H22ClN

Molecular Mass:
215.763 g/mol

Indications:
Treatment of moderate to severe dementia of the Alzheimer's type

Possible Mechanisms of Action:
Memantine is a moderate affinity, voltage-dependent, noncompetitive NMDA receptor antagonist (4). Memantine is also a voltage-dependent, reversible, noncompetitive antagonist at serotonin 5-HT3 receptors (5, 6). In addition, memantine acts as a noncompetitive open channel blocker at some subtypes of neuronal nicotinic acetylcholine receptors, including alpha4beta2 subunit-containing receptors (7) and alpha7 subunit-containing receptors (10).

Chemical Class:
cyclic amine

PubChem 2D Structure:

Generic Name:
rivastigmine tartrate

Trade Name:
Exelon ® [Novartis]

IUPAC Name:
[3-(1-dimethylaminoethyl)
phenyl] (ethyl-methyl-
amino)methanoate; 2,3-
dihydroxybutanedioic acid

Major Metabolite:
NAP 226-90


Dosage Forms/Routes:
Capsule/oral;
Solution/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
04/21/2000


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[
Link]

Epocrates:
[Link]

Empirical Formula:
C18H28N2O8

Molecular Mass:
400.424 g/mol

Indications:
Treatment of mild to moderate dementia of the Alzheimer's type

Possible Mechanisms of Action:
Rivastigmine is a slowly reversible (pseudo-irreversible) inhibitor of acetylcholinesterase and butyrylcholinesterase (8). Rivastigmine inhibits acetylcholinesterase in a noncompetitive manner (9).

Chemical Class:
carbamate derivative

PubChem 2D Structure:

Generic Name:
tacrine hydrochloride

Trade Name:
Cognex ® [First Horizon]

Common Chemical Name:
1,2,3,4-tetrahydro-9-
acridinamine monohydrochloride monohydrate

Major Metabolites:
1-hydroxytacrine

Dosage Forms/Routes:
Capsule/oral

Database Search Links:
[PubMed]

[Search PubMed for
Randomized Controlled Trials
]

[
PubChem]
[PDSP Ki database]

Initial Approval:
09/09/1993


Manufacturers:

[FDA Search]

Product Insert:
[Link]

RxList:
[
Link]

Epocrates:
[Link]

Empirical Formula:
C13H14N2•HCl
•H2O

Molecular Mass:
252.74 g/mol

Indications:
Treatment of mild to moderate dementia of the Alzheimer's type

Possible Mechanisms of Action:
Tacrine is a reversible acetylcholinesterase inhibitor (1). Tacrine is a mixed type inhibitor of acetycholinesterase, meaning that it exhibits both noncompetitive and competitive components of inhibition (1). Tacrine is also a reversible inhibitor of butyrylcholinesterase (1).

Chemical Class:
acridine derivative

2D Structure:

References:

1. Snape MF, Misra A, Murray TK, De Souza RJ, Williams JL, Cross AJ, Green AR.
A comparative study in rats of the in vitro and in vivo pharmacology of the acetylcholinesterase inhibitors tacrine, donepezil and NXX-066.
Neuropharmacology. 1999 Jan;38(1):181-93. [Abstract]

2. Lilienfeld S.
Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease.
CNS Drug Rev. 2002 Summer;8(2):159-76. [Abstract]

3. Samochocki M, Zerlin M, Jostock R, Groot Kormelink PJ, Luyten WH, Albuquerque EX, Maelicke A.
Galantamine is an allosterically potentiating ligand of the human alpha4/beta2 nAChR.
Acta Neurol Scand Suppl 2000;176:68-73 [Abstract]

4. Mobius HJ.
Pharmacologic rationale for memantine in chronic cerebral hypoperfusion, especially vascular dementia.
Alzheimer Dis Assoc Disord. 1999 Oct-Dec;13 Suppl 3:S172-8. [Abstract]

5. Reiser G, Binmoller FJ, Koch R.
Memantine (1-amino-3,5-dimethyladamantane) blocks the serotonin-induced depolarization response in a neuronal cell line.
Brain Res. 1988 Mar 8;443(1-2):338-44. [Abstract]

6. Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG.
The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner.
Neurosci Lett. 2001 Jun 22;306(1-2):81-4. [Abstract]

7. Buisson, Bruno, Bertrand, Daniel
Open-Channel Blockers at the Human alpha 4beta 2 Neuronal Nicotinic Acetylcholine Receptor
Mol Pharmacol 1998 53: 555-563 [Full Text]

8. Poirier J.
Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action.
Int J Clin Pract Suppl. 2002 Jun;(127):6-19. [Abstract]

9. Spencer CM, Noble S.
Rivastigmine. A review of its use in Alzheimer's disease.
Drugs Aging. 1998 Nov;13(5):391-411. [Abstract]

10. Aracava Y, Pereira EF, Maelicke A, Albuquerque EX.
Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons.
J Pharmacol Exp Ther. 2005 Mar;312(3):1195-205. [Abstract]