Delving into the Latest Updates on Etilevodopa with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Etilevodopa (USAN/INN), TV 1203, TV-1203

Target

DRDs

Mechanism

DRDs agonists(Dopamine receptors agonists)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Parkinson Disease

Originator Organization

The Hebrew University of Jerusalem

Active Organization-

Inactive Organization

Teva Pharmaceutical Industries Ltd.

The Hebrew University of Jerusalem

H. Lundbeck A/S

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC11H15NO4

InChIKeyNULMGOSOSZBEQL-QMMMGPOBSA-N

CAS Registry37178-37-3

Animal models have demonstrated the role of dopamine in regulating axial elongation, the critical feature of myopia. Because frequent delivery of dopaminergic agents via peribulbar, intravitreal, or intraperitoneal injections is not clinically viable, we sought to evaluate ocular penetration and safety of the topically applied dopaminergic prodrug etilevodopa.

Methods:

The ocular penetration of dopamine and dopaminergic prodrugs (levodopa and etilevodopa) were quantified using an enzyme-linked immunosorbent assay in enucleated porcine eyes after a single topical administration. The pharmacokinetic profile of the etilevodopa was then assessed in rats. A four-week once-daily application of etilevodopa as a topical eye drop was conducted to establish its safety profile.

Results:

At 24 hours, the studied prodrugs showed increased dopaminergic derivatives in the vitreous of porcine eyes. Dopamine 0.5% (P = 0.0123) and etilevodopa 10% (p = 0.370) achieved significant vitreous concentrations. Etilevodopa 10% was able to enter the posterior segment of the eye after topical administration in rats with an intravitreal half-life of eight hours after single topical administration. Monthly application of topical etilevodopa showed no alterations in retinal ocular coherence tomography, electroretinography, caspase staining, or TUNEL staining.

Conclusions:

At similar concentrations, no difference in ocular penetration of levodopa and etilevodopa was observed. However, etilevodopa was highly soluble and able to be applied at higher topical concentrations. Dopamine exhibited both high solubility and enhanced penetration into the vitreous as compared to other dopaminergic prodrugs.

Translational Relevance:

These findings indicate the potential of topical etilevodopa and dopamine for further study as a therapeutic treatment for myopia.

01 Jul 2009·Current aging science

Homology Modeling of Adenosine A2A Receptor and Molecular Docking for Exploration of Appropriate Potent Antagonists for Treatment of Parkinsons Disease

Article

Author: Somvanshi, Pallavi ; Singh, Vijai

Parkinson's disease (PD) is a neurodegenerative disorder of central nervous system (CNS) that impaired the patient motor skills, speech and other functions. Adenosine A2A receptors have a unique cellular distribution in the neuron, which is used as a potential target for PD. Homology modeling was used to construct the 3-D structure of A2A using the known template (PDB: 2VT4), and the stereochemical quality was validated. Several effective antagonist drugs were selected and active amino acid residues in A2A were targeted on the basis of robust binding affinity between protein-drug interactions in molecular docking. Six antagonists, Bromocriptine, Cabergoline, Etilevodopa, Lysuride, Melevodopa and Pramipexole, were found more potent for binding and the active amino acids residues were identified (http://www.rcsb.org/pdb/) in A2A receptor. It could be used as the basis for rationale designing of novel antagonist drugs against Parkinson's disease.

01 Feb 2006·Archives of neurology

A Randomized Controlled Trial of Etilevodopa in Patients With Parkinson Disease Who Have Motor Fluctuations

Article

Author: Eyal, Eli ; Sayag, Naim ; Goetz, Christopher ; Oakes, David ; Kieburtz, Karl ; Goren, Sari ; Scolnik, Marisa ; Nutt, John ; Blindauer, Karen ; Levy, Ruth ; Schwid, Steven ; Fahn, Stanley ; Salzman, Phyllis ; Stern, Matthew ; Shoulson, Ira ; Pagano, Mary

BACKGROUND:

Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration.

OBJECTIVE:

To determine the efficacy, safety, and tolerability of etilevodopa in patients with PD who have motor fluctuations.

DESIGN:

A double-blind, randomized, comparative clinical trial.

SETTING:

Forty-four sites in the United States and Canada.

PATIENTS:

Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing.

INTERVENTION:

Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks.

MAIN OUTCOME MEASURE:

Change from baseline in total daily TTON as measured using home diaries.

RESULTS:

The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopa-carbidopa group and 0.79 hour in the levodopa-carbidopa group (P = .24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P = .20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias.

CONCLUSION:

Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa.

100 Deals associated with Etilevodopa

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