Drugs used in Parkinsonism 123
Parkinsonism is an extrapyramidal motor
disorder, characterized by akinesia, rigidity
and tremor with secondary manifestations
such as excessive salivation, seborrhoea,
mood changes (especially depression) and
in certain patients, liver damage has been
reported. It was first described by James
Parkinson in 1817.
In parkinsonism, there is a degeneration
of dopaminergic nerve endings of the basal
ganglion (neurons in substantia nigra and
the nigrostriatal tract), which results in
deficiency of dopamine and cholinergic
overactivity. This imbalance between the
dopamine deficiency and overactivity of
cholinergic system gives rise to this motor
disorder. Thus, the rational approach to the
therapy of parkinsonism would be either to
increase the central dopaminergic activity or
to decrease the central cholinergic activity.
The drugs used in the treatment of
parkinsonism can be classified as in table 2.10.1.
LEVODOPA
Levodopa is the most effective drug
available for the treatment of parkinsonism
and used in combination with peripheral
dopa decarboxylase inhibitors. Levodopa as
such is inactive but it is the immediate
precursor of the transmitter dopamine.
When administered orally, 95 percent of the
dose is decarboxylated in the peripheral
tissues (mainly in liver). Dopamine thus
formed in peripheral system act on CVS and
other peripheral tissues and produce the
unwanted effects. Dopamine, as such, can
not be used to treat parkinsonism as it does
not cross the blood brain barrier. However,
the precursor of dopamine i.e. dopa crosses
the blood brain barrier and is converted to
dopamine in the brain and is released as a
neurotransmitter.
Pharmacological Actions
- CNS: Levodopa does not produce any
significant action in normal individual.
In parkinsonism patient, it improves all
manifestations of parkinsonism.
Akinesia responds first, followed by
rigidity and tremor. Other symptoms
such as seborrhoea, sialorrhoea and
aphonia also improve. The drug also
improves mood, memory and patients
(Mode of Action of Drugs)