Pharmacology for Dentistry

126 Section 2/ Drugs Acting on CNS

AMANTADINE

It is an antiviral compound and also
improves akinesia, rigidity and tremor in
parkinsonism. It is more effective than
atropine like drugs but it is less effective
than levodopa. Its effect on tremors is less
than on rigidity. It acts by releasing
dopamine from the neuronal storage sites.
The drug is well absorbed orally and
excreted unchanged in urine and drug is
tolerated well and cause fewer adverse
effects. In toxic dose, it causes convulsions
and mania and should be used cautiously
in epileptic patients.

SELEGILINE

It is a selective MAO-B inhibitor, which
is predominant in brain and blood platelets.
It retards intracerebral degradation of
dopamine. It is used with levodopa in early
cases of parkinsonism. It prolongs levodopa
action, attenuates motor fluctuations and
decreases wearing off effect. But clinical
benefits are short lived (6-24 months).

Adverse effects are postural hypotension,
nausea, confusion, increased levodopa in-
duced involuntary movements and confusion.

DRUGS ACTING ON CENTRAL

ANTICHOLINERGIC SYSTEM

The cholinergic neurons are immediately
distal to dopaminergic fibres in the cau-
date nucleus in brain. They are excitatory
and in parkinsonism, there is a degenera-
tion of inhibitory dopaminergic neurons
and thus, there is increased cholinergic ac-
tivity (preponderance of cholinergic sys-
tem) which results in the symptoms of par-
kinsonism.

The central anticholinergic drugs having

a higher central versus peripheral

cholinergic action ratio are useful. The drugs

like atropine are much less effective than

levodopa but they are used when levodopa

is not tolerated or contraindicated or the

patient is not benefitted by levodopa or drug

induced parkinsonism.

Atropine like drugs antagonize the

rigidity and akinesia and cause reduction

in the intensity of tremors. They act by

reducing the unbalanced cholinergic

activity in parkinsonism. Benzhexol is

most commonly used and effective drug

among the atropine substitutes used in

parkinsonism.

Atropine like drugs cause several side

effects such as dry mouth, blurred vision,

urinary retention, mental confusion,

hallucinations etc.

Antihistaminics are better tolerated by

elderly patients who do not tolerate

anticholinergics. Antihistaminics do not

cause blurring of vision and xerostomia and

also possess some central anticholinergic

properties.

NEWER DRUGS

ROPINIROLE

Ropinirole is a non-ergot dopamine

agonist with high relative in vitro specificity

and full intrinsic activity at the D 2 and D 3

dopamine receptor subtypes, binding with

higher affinity to D 3 than to D 2 or D 4 receptor

subtypes. Ropinirole is more specific than

dopamine agonists, bromocriptine and

pergolide. The relevance of D 3 receptor

binding in Parkinson’s disease is unknown.