Generic Name:
amantadine hydrochloride

Trade Name:
Symmetrel ® [Endo]

IUPAC Name:
adamantan-1-amine hydrochloride

Dosage Forms/Routes:
Tablet/oral;
Syrup/oral;
Capsule/oral

Major Metabolite:
acetylamantadine

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
11/03/1980

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₁₀H₁₈ClN

Molecular Mass:
187.709 g/mol

Indications:
Amantadine is indicated in the treatment of parkinsonism and drug-induced extrapyramidal reactions. Amantadine is also indicated for the prophylaxis and treatment of signs and symptoms of infection caused by various strains of influenza A virus.

Possible Mechanisms of Action:
At NMDA receptors, amantadine stabilizes closed channel states by accelerating channel closure; it also inhibits current flow through open NMDA receptor channels to a lesser degree (1). Amantadine's effects on NMDA receptors are greatest in the striatum (2). The drug may also decrease the rate of reactivation and act as a noncompetitive open channel blocker at nicotinic acetylcholine receptors such as those that contain the alpha7 subunit (3). In addition, amantadine is a weak agonist at sigma-1 receptors (4). Amantadine's antiviral utility results from its blockade of the influenza A virus M2 membrane protein (5). M2 proteins form proton-selective ion channels (6).

Chemical Class:
tricyclic amine

PubChem 2D Structure:

Generic Name:
apomorphine hydrochloride

Trade Name:
Apokyn ® [Mylan Bertek]

Common Chemical Name:
6ab-Aporphine-10,11-diol
hydrochloride hemihydrate

Dosage Forms/Routes:
Injectable/subcutaneous

Major Metabolite:
8-oxo-apomorphine-
semiquinone

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
04/20/2004

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₃₄H₃₈Cl₂N₂O₅

Molecular Mass:
625.581 g/mol

Indications:
Apomorphine is indicated for the acute, intermittent treatment of hypomobility, "off" episodes ("end-of-dose wearing off" and unpredictable "on/off" episodes) associated with advanced Parkinson’s disease. Apomorphine has been studied as an adjunct to other medications (see CLINICAL PHARMACOLOGY: Clinical Trials in the prescribing information).

Chemical Class:
aporphine alkaloid of the dibenzoquinoline class

PubChem 2D Structure:

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

Generic Name:
benztropine mesylate

Trade Name:
Cogentin ® [Merck]

IUPAC Name:
3-benzhydryloxy-8-methyl-8-
azabicyclo[3.2.1]octane;
methanesulfonic acid

Dosage Forms/Routes:
Tablet/oral;
Injectable/injection

Major Metabolites:
N-desmethylbenztropine;
benztropine N-oxide

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
03/05/1954

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₂₂H₂₉NO₄S

Molecular Mass:
403.536 g/mol

Indications:
Benztropine is indicated for use as an adjunct in the therapy of all forms of parkinsonism. The drug is also useful in the control of extrapyramidal disorders (except tardive dyskinesia) due to neuroleptic drugs (e.g., phenothiazines).

Chemical Class:
tropanol derivative

PubChem 2D Structure:

Generic Name:
biperiden hydrochloride

Trade Name:
Akineton ® [Abbott, Par]

IUPAC Name:
1-(5-bicyclo[2.2.1]hept-2-
enyl)-1-phenyl-3-(1-
piperidyl)propan-1-ol
hydrochloride

Dosage Forms/Routes:
Tablet/oral

Major Metabolites:
Unknown

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
09/08/1959

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₂₁H₃₀ClNO

Molecular Mass:
347.922 g/mol

Indications:
Benztropine is indicated for use as an adjunct in the therapy of all forms of parkinsonism (idiopathic, postencephalitic, arteriosclerotic). The drug is also useful in the control of extrapyramidal disorders due to neuroleptic drugs (e.g. phenothiazines).

PubChem 2D Structure:

Generic Name:
bromocriptine mesylate

Trade Name:
Parlodel ® [Novartis]

Common Chemical Name:
ergotaman-3’,6’,18-trione,2-
bromo-12'-hydroxy-2'- (1-
methylethyl)-5'-(2-
methylpropyl)-,(5'a)
monomethanesulfonate (salt)

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

Major Metabolites:
2-bromolysergic acid;
2-bromoisolysergic acid

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
06/28/1978

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₃₃H₄₄BrN₅O₈S

Molecular Mass:
750.701 g/mol

Possible Mechanisms of Action:
Bromocriptine is an agonist at dopamine D2 and D3 receptors (7, 10). Bromocriptine also binds to alpha-1A-adrenoceptors, alpha-1B-a drenoceptors, alpha-1D-adrenoceptors, alpha-2A-adrenoceptors, alpha-2B-adrenoceptors, and alpha-2C-adrenoceptors (10). The drug may also bind to serotonin 5-HT1A (10), 5-HT1D (10), 5-HT2B (10), and 5-HT7 receptors (17). In addition, bromocriptine may accelerate the transport of glutamate mediated by hGluT-1 (29). The drug is also a potent free radical scavenger (30).

Indications:
Bromocriptine mesylate is in the treatment of the signs and symptoms of idiopathic or postencephalitic Parkinson’s disease. As adjunctive treatment to levodopa (alone or with a peripheral decarboxylase inhibitor), bromocriptine mesylate therapy may provide additional therapeutic benefits in those patients who are currently maintained on optimal dosages of levodopa, those who are beginning to deteriorate (develop tolerance) to levodopa therapy, and those who are experiencing “end of dose failure” on levodopa therapy. Bromocriptine mesylate therapy may permit a reduction of the maintenance dose of levodopa and, thus may ameliorate the occurrence and/or severity of adverse reactions associated with long-term levodopa therapy such as abnormal involuntary movements (e.g., dyskinesias) and the marked swings in motor function (“on-off” phenomenon). Continued efficacy of bromocriptine mesylate therapy during treatment of more than 2 years has not been established.

Data are insufficient to evaluate potential benefit from treating newly diagnosed Parkinson’s disease with bromocriptine mesylate. Studies have shown, however, significantly more adverse reactions (notably nausea, hallucinations, confusion and hypotension) in bromocriptine mesylate treated patients than in levodopa/carbidopa treated patients. Patients unresponsive to levodopa are poor candidates for bromocriptine mesylate therapy.

See the prescribing information for information about indications related to hyperprolactinemia-associated dysfunctions and acromegaly.

Chemical Class:
ergot derivative

PubChem 2D Structure:

Generic Name:
carbidopa

Trade Name:
Lodosyn ® [Bristol-Myers Squibb]

IUPAC Name:
3-(3,4-dihydroxyphenyl)-2-
hydrazinyl-2-methyl-propanoic
acid hydrate

Dosage Forms/Routes:
Tablet/oral

Major Metabolites:
a-methyl-3-methoxy-4-
hydroxyphenylpropionic acid;
a-methyl-3,4-
dihydroxyphenylpropionic acid

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
04/25/1977

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₁₀H₁₆N₂O₅

Molecular Mass:
244.245 g/mol

Possible Mechanisms of Action:
Carbidopa is a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor (18). The drug, which does not cross the blood-brain barrier, is combined with levodopa to prevent its conversion to dopamine in the periphery (18).

Indications:
Lodosyn is indicated for use with Sinemet (carbidopa-levodopa) or with levodopa in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), postencephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication.

Lodosyn is for use with Sinemet (carbidopa-levodopa) in patients for whom the dosage of SINEMET (carbidopa-levodopa) provides less than adequate daily dosage (usually 70 mg daily) of carbidopa.

Lodosyn is for use with levodopa in the occasional patient whose dosage requirement of carbidopa and levodopa necessitates separate titration of each entity.

Lodosyn is used with Sinemet (carbidopa-levodopa) or with levodopa to permit the administration of lower doses of levodopa with reduced nausea and vomiting, more rapid dosage titration, and with a somewhat smoother response. However, patients with markedly irregular ("on-off") responses to levodopa have not been shown to benefit from the addition of carbidopa.

Since carbidopa prevents the reversal of levodopa effects caused by pyridoxine, supplemental pyridoxine (vitamin B6), can be given to patients when they are receiving carbidopa and levodopa concomitantly or as Sinemet (carbidopa-levodopa).

Although the administration of Lodosyn permits control of parkinsonism and Parkinson's disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than in reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa.

Certain patients who responded poorly to levodopa alone have improved when carbidopa and levodopa were given concurrently. This was most likely due to decreased peripheral decarboxylation of levodopa rather than to a primary effect of carbidopa on the peripheral nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa.

In considering whether to give Lodosyn with Sinemet (carbidopa-levodopa) or with levodopa to patients who have nausea and/or vomiting, the physician should be aware that, while many patients may be expected to improve, some may not. Since one cannot predict which patients are likely to improve, this can only be determined by a trial of therapy. It should be further noted that in controlled trials comparing carbidopa and levodopa with levodopa alone, about half the patients with nausea and/or vomiting on levodopa alone improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.

PubChem 2D Structure:

Generic Name:
carbidopa, entacapone, and levodopa

Trade Name:
Stalevo ® [Orion]

IUPAC Name:
3-(3,4-dihydroxyphenyl)-2-
hydrazinyl-2-methyl-propanoic
acid hydrate; 2-cyano-3-(5-
dihydroxyamino-3,4-dioxo-1-
cyclohexa-1,5-dienyl)-N,N-
diethyl-prop-2-enamide;
2-amino-3-(3,4-dihydroxyphenyl)-
propanoic acid

Dosage Forms/Routes:
Tablet/oral

Major Metabolites:
Carbidopa:
a-methyl-3-methoxy-4-
hydroxyphenylpropionic acid;
a-methyl-3,4-
dihydroxyphenylpropionic acid
Entacapone:
cis-entacapone;
entacapone glucuronide
Levodopa:
dopamine;
homovanillic acid

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]

Initial Approval:
06/11/2003

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Indications:
Stalevo (carbidopa, levodopa and entacapone) is indicated to treat patients with idiopathic Parkinson’s disease:

1. To substitute (with equivalent strength of each of the three components) for immediate-release carbidopa/levodopa and entacapone previously administered as individual products.

2. To replace immediate-release carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose "wearing-off" (only for patients taking a total daily dose of levodopa of 600 mg or less and not experiencing dyskinesias, see DOSAGE AND ADMINISTRATION in the prescribing information).

Possible Mechanisms of Action:
Levodopa is the immediate precursor to dopamine. Entacapone is a selective, reversible catechol-O-methyltransferase (COMT) inhibitor that increases the bioavailability of levodopa (19). Entacapone does not cross the blood-brain barrier (20). Carbidopa is a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor (18). Carbidopa, which also does not cross the blood-brain barrier, is combined with levodopa to prevent its conversion to dopamine in the periphery (18).

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

Generic Name:
carbidopa and levodopa

Trade Name:
Sinemet ® [Bristol-Myers Squibb]

IUPAC Name:
3-(3,4-dihydroxyphenyl)-2-
hydrazinyl-2-methyl-propanoic
acid; 2-amino-3-(3,4-
dihydroxyphenyl)-propanoic acid

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

Major Metabolites:
Carbidopa:
a-methyl-3-methoxy-4-
hydroxyphenylpropionic acid;
a-methyl-3,4-
dihydroxyphenylpropionic acid
Levodopa:
dopamine;
homovanillic acid

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]

Initial Approval:
05/02/1975

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₁₉H₂₅N₃O₈

Molecular Mass:
423.417 g/mol

Possible Mechanisms of Action:
Levodopa is the immediate precursor to dopamine. Carbidopa is a peripheral aromatic L-amino acid decarboxylase (AADC) inhibitor (18). Carbidopa, which does not cross the blood-brain barrier, is combined with levodopa to prevent its conversion to dopamine in the periphery (18).

Indications:
Sinemet is indicated in the treatment of the symptoms of idiopathic Parkinson's disease (paralysis agitans), post-encephalitic parkinsonism, and symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication and/or manganese intoxication. Sinemet is indicated in these conditions to permit the administration of lower doses of levodopa with reduced nausea and vomiting, with more rapid dosage titration, with a somewhat smoother response, and with supplemental pyridoxine (vitamin B6).

In some patients a somewhat smoother antiparkinsonian effect results from therapy with Sinemet than with levodopa. However, patients with markedly irregular ("on-off") responses to levodopa have not been shown to benefit from Sinemet.

Although the administration of carbidopa permits control of parkinsonism and Parkinson's disease with much lower doses of levodopa, there is no conclusive evidence at present that this is beneficial other than in reducing nausea and vomiting, permitting more rapid titration, and providing a somewhat smoother response to levodopa.

Certain patients who responded poorly to levodopa have improved when Sinemet was substituted. This is most likely due to decreased peripheral decarboxylation of levodopa which results from administration of carbidopa rather than to a primary effect of carbidopa on the nervous system. Carbidopa has not been shown to enhance the intrinsic efficacy of levodopa in parkinsonian syndromes.

In considering whether to give Sinemet to patients already on levodopa who have nausea and/or vomiting, the practitioner should be aware that, while many patients may be expected to improve, some do not. Since one cannot predict which patients are likely to improve, this can only be determined by a trial of therapy. It should be further noted that in controlled trials comparing Sinemet with levodopa, about half of the patients with nausea and/or vomiting on levodopa improved spontaneously despite being retained on the same dose of levodopa during the controlled portion of the trial.

PubChem 2D Structure:

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

Generic Name:
entacapone

Trade Name:
Comtan ® [Orion (marketed by Novartis)]

IUPAC Name:
2-cyano-3-(5-dihydroxyamino-
3,4-dioxo-1-cyclohexa-1,5-
dienyl)-N,N-diethyl-prop-2-
enamide

Dosage Forms/Routes:
Tablet/oral

Major Metabolites:
cis-entacapone;
entacapone glucuronide

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
10/19/1999

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₁₄H₁₅N₃O₅

Molecular Mass:
305.286 g/mol

Indications:
Comtan is indicated as an adjunct to levodopa / carbidopa to treat patients with idiopathic Parkinson’s Disease who experience the signs and symptoms of end-of-dose “wearing-off” (see CLINICAL PHARMACOLOGY: Clinical Studies in the prescribing information).

Comtan’s effectiveness has not been systematically evaluated in patients with idiopathic Parkinson’s Disease who do not experience end-of-dose “wearing-off.”

Chemical Class:
nitrocatechol

PubChem 2D Structure:

Generic Name:
pergolide mesylate

Trade Name:
Permax ® [Eli Lilly]

Common Chemical Name:
8B-[(Methylthio)methyl]-6-
propylergoline
monomethanesulfonate

Dosage Forms/Routes:
Tablet/oral

Major Metabolites:
pergolide sulfone;
pergolide sulfoxide;
despropyl pergolide;
despropyl pergolide sulfoxide

Database Search Links:
[PubMed]
[Search PubMed for
Randomized Controlled Trials]
[PubChem]
[PDSP K_i database]

Initial Approval:
12/30/1988

Manufacturers:
[FDA Search]

Prescribing Information:
[Link]

RxList:
[Link]

Epocrates:
[Link]

Empirical Formula:
C₂₀H₃₀N₂O₃S₂

Molecular Mass:
410.596 g/mol

Indications:
Permax is indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson’s disease.

Evidence to support the efficacy of pergolide mesylate as an antiparkinsonian adjunct was obtained in a multicenter study enrolling 376 patients with mild to mode