Brain Diseases and Disorders
13
be gradually increased, and domperidone (a peripheral dopamine antagonist)
may need to be used. Agonists also experience more central side effects than
levodopa, including mental and cognitive side effects. Serious issues might
arise in the form of hallucinations and psychotic symptoms [70]. To improve
the effectiveness of levodopa or dopamine agonists various strategies such as
adding another dopamine agonist, dividing the dose of levodopa into smaller
but more frequent doses, or adding a catechol-O-methyltransferase inhibitor
or monoaminoxidase (MAO) inhibitors are frequently applied [54, 55].
Amantadine is synthetic tricyclic amine manufactured as salt, as imme-
diate or extended-release oral formulations and as intravenous (IV) infusion
[71]. Although it has been suggested for PD, this drug is not as potent as any
other dopaminergic medication. It is hypothesized that it works by enhancing
dopamine release from vesicles, blocking dopamine absorption from the synap-
tic cleft, and having an anticholinergic effect. Livedo reticularis, or red, mot-
tled skin around the knees, ankle edema, visual hallucinations, and confusion
are common adverse effects of amantadine [72]. Anticholinergic medications
are expected to work by reversing the imbalance caused by lower dopamine
levels between acetylcholine and striatal dopamine activity. They have a mi-
nor impact on PD symptoms, and there is currently inadequate evidence to
support its specific effect on the tremors [73]. Due to their modest anticholin-
ergic and hypnotic properties, antihistamines like diphenhydramine can also
be utilized, particularly in elderly individuals for whom anticholinergics are
contraindicated [73]. Dry mouth, constipation, urine retention, tachycardia,
and hazy vision from trouble adapting are examples of peripheral adverse
effects of anticholinergics [74].
1.6.3
Huntington’s Disease (HD)
The neurodegenerative condition known as Huntington’s disease (HD) is an
autosomal dominant condition that manifests as physical, cognitive, and men-
tal symptoms emerging in middle age [75]. Chorea—unusual, uncontrollable
movement—is the most definitive sign of HD. A substantial portion of the
body is involved in these uncontrollable moving jumps that occur continu-
ously [76]. HD is marked by abnormal facial expressions, expression disorder,
and difficulty swallowing and chewing due to physical instability and weak-
ening of muscle function. Dysphagia and related weight loss are also present.
Moreover, irregularities in sleep cycles, insomnia, and fast eye movements
during sleep are noted [77]. Given that the condition is inherited autosomal
dominantly, inheriting the mutant gene from one parent who has been diag-
nosed with HD carries a 50% risk. This danger is alarmingly high given the
progressive nature and the lack of a conclusive cure for the disease at present
[78].
The neuropathology of HD shows that different areas of the brain are
affected by the disease to diverse degrees [79]. Patients with HD have impaired
glucose metabolism, especially in the striatum, according to PET imaging