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Individual Drugs


  1. Levodopa
    1. Prodrug
    2. Introduced by Hornequez & Cotzias’1962
    3. Precursor of DA
    4. Hypokinesia and rigidity resolve first, later tremor as well. Secondary symptoms of posture, gait, handwriting, speech, facial expression, mood, self care and interest in life are gradually normalized.
    5. A common problem is the development of the “wearing off” phenomenon: each dose of levodopa effectively improves mobility for a period of time, perhaps 1–2 hours, but rigidity and akinesia return rapidly at the end of the dosing interval. In the later stages of PD, patients may fluctuate rapidly between being “off,” having no beneficial effects from their medications, and being “on” but with disabling dyskinesias, a situation called the on/off phenomenon.


  1. Well absorbed; metabolized in intestinal wall
  2. Half life=8 hours
  3. Actively transported
  4. Metabolized in liver to O-HMD
  5. Absorption is reduced by protein meals


  1. MC
    i.  Nausea        
    ii. Vomiting              
    iii. Postural hypotension   
    iv. Arrhythmias        
    v.  Hallucinations             
    vi. Dyskinesias (On & off phenomena)
  2. Dyskinesia are best improved by amantidine

C/I of L-dopa

  1. Acute narrow angle glaucoma        
  2. Peptic ulcer                
  3. Malignant melanoma


  1. L-Dopa MUST NEVER given with D-2 blockers
  2. Not to be given with:
    i. TCADs          
    ii. MAO-B-1/non specific MAO inhibitor      
    iii. B6 (Pyridoxine)   

Carbidopa (and Benserazide)

  • Peripheral decarboxylase inhibitors-
  • Administered along with levodopa, it increase its t1/2 in periphery and make more of it available to cross blood-brain barrier to reach its site of action. Also it reduces Levodopa dose to one fourth.


  1. Increases duration
  2. Increases bioavailability
  3. Dose of levodopa is reduced
  4. Nausea & vomiting is less
  5. Reduces cardiac effects of levodopa
  6. On-off effects are minimized
  7. Pyridoxine reversal do not occur


  1. Psychiatric side effects are more
  2. Postural hypotension pronounced
  3. Involuntary movements increased
  1. Amantidine
    1. Anti-Influenza A2 drug
    2. Dopamine transmission enhancer, NMDA glutamate effect is more important.
    3. Used as adjunct with levodopa-suppress motor fluctuation and involuntary movements
    4. Short acting (half life 2 hours)
    5. Eliminated unchanged
      1. C/I-Renal failure
      2. Psychiatric patients
      3. Epilepsy


  1. Livedo Reticularis (due to local CA release)
  2. Ankle edema- diuretic responsive
  1. Dopamine agonists

DA Agonist vs Levodopa

1) Since enzymatic conversion of these drugs is not required for activity, they do not depend on the functional capacities of the nigrostriatal neurons.

2) Most dopamine-receptor agonists in clinical use have durations of action substantially longer than that of levodopa and are useful in the management of dose-related fluctuations in motor state.

3) Finally, if free radical formation from dopamine metabolism actually contributes to neuronal death, then dopamine-receptor agonists may modify the course of the disease by reducing endogenous release of dopamine as well as the need for exogenous levodopa.


  1. Pergolide    
  2. Piribidil                
  3. Apomorphine   
  4. Lergotrile            
  5. Rotigotine (Patch)-non-ergot derivative
  • D1 agonist
  1. Short acting
  2. Well absorbed
  3. High first pass metabolism
  4. All cause nausea
  5. Other s/e-Postrual hypotension
  6. Risk of Psychiatric side effects are more compared to l-dopa


Direct agonist at D3 receptors.

Reduces symptoms of parkinsonism and smooths out fluctuations in levodopa response. Can be used as initial therapy

Also effective in on-off phenomenon.

Nausea and vomiting, postural hypotension, dyskinesias, confusion, impulse control disorders, sleepiness.


Similar to pramipexole

nonergot; relatively pure D2 agonist


Ergot derivative; potent agonist at D2 receptors

More toxic than pramipexole or ropinirole

Now rarely used for antiparkinsonian effect


Nonergot; subcutaneous route useful for rescue treatment (FREEZING episodes) in levodopa-induced dyskinesia; high incidence of nausea and vomiting

Also used for impotence

  1. Levodopa best improves bradykinesia
  2. DOC-drug induced Parkinson’s disease
  1. COMT Inhibitors
    1. Tolcapone
    2. Entacapone
      1. Inhibit dopamine degradation
      2. Tolcapone-central
      3. Entacapone-both central+peripheral
      4. Tolcapone-more potent; entacapone is less potent
    3. Drug combination like Levodopa+carbidopa+entacapone used in advanced PD
    4. Tolcapone-hepatotoxic, Rhabdomyolysis
    5. Entacapone accumulates in renal failure
  2. MAO inhibitors
  • Two isoenzyme forms of MAO, termed MAO-A and MAO-B are recognized; both are present in peripheral adrenergic structures and intestinal mucosa, while the latter (MAO-B) predominates in the brain and blood platelets. Monoamine oxidase A metabolizes norepinephrine, serotonin, and dopamine; monoamine oxidase B metabolizes dopamine selectively.
  • The combined administration of levodopa and an inhibitor of both forms of monoamine oxidase (ie, a nonselective inhibitor) must be avoided, because it may lead to Hypertensive Crises, because of the peripheral accumulation of norepinephrine.


In low dose is selective inhibitor of MAO-B.

Retards the breakdown of dopamine; in consequence, it enhances and prolongs the antiparkinsonism effect of levodopa (thereby allowing the dose of levodopa to be reduced) and may reduce mild on-off or wearing-off phenomena. It is therefore used as adjunctive therapy for patients with a declining or fluctuating response to levodopa.

Probably Neuroprotective, by free radicals generated by metabolism of MAO on dopamine.


More potent than Seligine.


Drug interactions

  • Neither selegiline nor rasagiline should be taken by patients receiving meperidine, tramadol, methadone, propoxyphene, cyclobenzaprine, or St. John’s wort.
  • Rasagiline or selegiline should be used with care in patients receiving tricyclic antidepressants or serotonin reuptake inhibitors because of the risk of acute toxic interactions of the serotonin syndrome type.

Anticholinergic Drugs

  • These are drugs having a higher central: peripheral anticholinergic action ratio than atropine, but the pharmacological profile is similar to it. In addition, certain H1 antihistaminics have significant central anticholinergic property.
  • These agents may improve the tremor and rigidity of Parkinsonism but have little effect on bradykinesia.
  • Acute suppurative parotitis sometimes occurs as a complication of dryness of the mouth.
  • Anticholinergics are the only drugs effective in drug (phenothiazine) induced Parkinsonism. They may be used alone in mild cases and when levodopa is contraindicated. In others, they can be combined with levodopa in an attempt to lower its dose.

Other Movement Disorders

Huntingtons Disease

Opposite to PD, because of increased responsiveness of post- synaptic dopamine receptors or deficiency of a neurotransmitter that normally antagonizes dopamine.

Drugs that impair dopaminergic neurotransmission, either by depleting central monoamines (eg, reserpine, tetrabenazine) or by blocking dopamine receptors (eg, phenothiazines, butyrophenones), often alleviate chorea, whereas dopamine-like drugs such as levodopa tend to exacerbate it.

DRUGS: Reserpine, tetrabenazine, haloperidol, olanzapine


Physiologic postural tremor: Normal phenomenon is enhanced in amplitude by anxiety, fatigue, thyrotoxicosis, and intravenous epinephrine or isoproterenol. Propranolol is the drug of choice.

Essential tremor: A postural tremor, sometimes familial with autosomal dominant inheritance, which is clinically similar to physiologic tremor. Respond dramatically to standard doses of metoprolol as well as to propranolol. primidone, topiramate, gabapentin, alprazolam.

Intention tremor: Occurs as a toxic manifestation of alcohol or drugs such as phenytoin. Withdrawal or reduction in dosage provides dramatic relief. There is no satisfactory pharmacologic treatment for intention tremor due to other neurologic disorders.

Resting tremor: due to Parkinsons disease


Benign hereditary chorea: symptomatic treatment

Drug-induced chorea is managed by withdrawal of the offending substance, which may be levodopa, an antimuscarinic drug, amphetamine, lithium, phenytoin, or an oral contraceptive.

Sydenham’s chorea is temporary and usually so mild that pharmacologic management of the dyskinesia is unnecessary, but dopamine-blocking drugs are effective in suppressing it.


Treatment with haloperidol, perphenazine, or other dopamine blocking drugs may be helpful.

Athetosis And Dystonia

There is no satisfactory medical treatment for them. A subset of patients respond well to levodopa medication (dopa-responsive dystonia), which is therefore worthy of trial. Occasional patients with dystonia may respond to diazepam, amantadine, antimuscarinic drugs (in high dosage), carbamazepine, baclofen, haloperidol, or phenothiazines.

Patients with focal dystonias such as blepharospasm or torticollis often benefit from injection of botulinum toxin into the overactive muscles.

Deep brain stimulation may be helpful in medically intractable cases.


Chronic multiple tics (Gilles de la Tourette’s syndrome): Guanfacine, Clonidine, Pimozide, Haloperidol.

Injection of botulinum toxin A at the site of problematic tics is sometimes helpful

Deep brain stimulation is sometimes worthwhile in otherwise intractable cases

Restless Leg Syndrome

Respond to dopamine agonists, levodopa, diazepam, clonazepam, gabapentin, or opiates (oxycodone). Dopaminergic therapy is the preferred treatment for restless legs syndrome and should be initiated with long-acting dopamine agonists (eg, Pramipexole or Ropinirole once daily)

Wilsons Disease

Traditionally, Penicillamine used to chelate excess copper. Adverse effects include nausea and vomiting, nephrotic syndrome, a lupus-like syndrome, pemphigus, myasthenia, arthropathy, optic neuropathy, and various blood dyscrasias. In about 10% of instances, neurologic worsening occurs with penicillamine.

Trientine hydrochloride, another chelating agent, is preferred by many over penicillamine because of the lesser likelihood of drug reactions or neurologic worsening.

Tetrathiomolybdate may be better than trientine for preserving neurologic function

Zinc acetate administered orally increases the fecal excretion of copper and can be used in combination with these other agents.

Liver transplantation is sometimes necessary.



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