They can also aid to open new avenues for centrally acting COMT inhibitors, and perhaps irreversible inhibitors, to be tested for PD and other neurological diseases.
The current pharmacological treatments for Parkinson's disease only offer symptomatic relief to the patients and are based on the administration of levodopa and catechol-O-methyltransferase or monoamine oxidase-B inhibitors (IMAO-B).
The results showed that dopamine (DA) in the form of a conjugate with TP10 evidently gained access to the brain tissue, exhibited low susceptibility to O-methylation reaction by catechol- O-methyltransferase (lower than that of DA), possessed a relatively high affinity to both dopamine D<sub>1</sub> and D<sub>2</sub> receptors (in the case of D<sub>1</sub>, a much higher than that of DA), and showed anti-parkinsonian activity (higher than that of l-DOPA) in the MPTP-induced preclinical animal model of PD.
The aim was to evaluate the efficacy of the catechol-O-methyltransferase inhibitor opicapone (25 and 50 mg) as adjunct therapy to levodopa in a pooled population of Parkinson's disease patients who participated in the pivotal double-blind trials of opicapone and their 1-year open-label extensions.
There is no cure for PD, and the pharmacological treatment acts as a dopaminergic supplement with levodopa, COMT inhibitors, anticholinergics agents, dopaminergic agonists, and inhibitors of MAO-B, which basically aim to control the symptoms, but enabling a better functional mobility, increasing the life expectancy of treated PD patients.
This study indicated a significantly closer association between COMTVal158Met polymorphism and PD in the Japanese and Indian populations compared with other ethnicities.
Opicapone is a catechol O-methyltransferase (COMT) inhibitor indicated for use as adjunct to levodopa therapy in patients with Parkinson's disease (PD) and motor fluctuations.
Currently, peripheral COMT inhibitors have an important role in the treatment of Parkinson's disease, and central COMT inhibitors have a potential role in the treatment of various neuropsychiatric disorders, such as attention deficit hyperactivity disorder.
These findings suggest that upregulation of COMT, likely resulting from DNA hypomethylation, in dopaminergic neurons may contribute to the initial stage of neuronal dysfunction in Parkinson's disease.
Opicapone fills the unmet need for a compound with sustained COMT inhibition which will improve levodopa bioavailability in patients with Parkinson's disease.
Moreover, an observed decrease in norepinephrine concentrations in the LC is consistent with the hypothesis that early-stage PD includes noradrenergic loss in the brainstem, and is congruent with a significant increase in catechol-O-methyltransferase expression in the LC of Pink1 -/- animals.
While the COMT <sup>158</sup> Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P = .023), the DRD2 <sup>957</sup> T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P < .001).
Some of the features corresponding to the genes such as COMT, DCTN1 and PRNP were uniquely identified by LR and are reported to play a significant role in PD.
We concluded that before beginning PD pharmacological treatment, it is important to consider the genetic variants of the MAO-B and COMT genes and the sex, reinforcing the evidence that sexual dimorphism in the genes related to dopamine metabolism might affect PD treatment.
The aim of this study is to investigate the association between seven COMT gene single-nucleotide polymorphisms (SNPs) and the development of LID in patients with PD.
Tolcapone, a drug commonly used in the treatment of Parkinson's disease, is a potent inhibitor of COMT and previous studies indicate that Tolcapone increases the bioavailability of dopamine in cells.