Background
Adults over the age of 60 with symptoms of major depressive disorder are said to have late-life depression (LLD), a condition that usually decreases a person's quality of life and is associated with other risks like physical frailty and dementia. A common feature of more severe LLD is psychomotor slowing, where a person's ability to think and move are impaired. For example, they might not be able to walk or process information as quickly, and they might have problems with their working memory.
Psychomotor slowing in LLD might be the result of a problem with the way a person's body produces or responds to the neurotransmitter dopamine. The drug Levodopa (L-DOPA), which can replace missing dopamine in the brain, has been used to treat to treat Parkinson's disease for many decades, and it might also affect psychomotor slowing in LLD.
Methods
In this study, participants are adults aged 60 years or older with moderate to severe major depression. Participants undergo the "L-DOPA challenge"-a 2-week period where they receive a dose of L-DOPA once a day for the first week and a dose of L-DOPA twice a day for the second week. Before and after a participant completes the L-DOPA challenge, the study team assesses their depressive symptoms and psychomotor function. After the L-DOPA challenge, if a participant still shows signs of moderate or severe depression, they receive an antidepressant for 12 weeks.
Aims
The first aim of this study is to test the feasibility of the L-DOPA challenge-that is, whether most of the 50 participants recruited for this study will complete the L-DOPA challenge. For example, participants might have to withdraw if they can't make the daily visits to the research site to receive their L-DOPA medication, if they can't tolerate the medication's side effects, or if their depressive symptoms get significantly worse. Our hypothesis is that 80% of the participants will complete the L-DOPA challenge.
The second aim of the study is to see if L-DOPA affects participants' depressive symptoms, processing speed, and working memory. Our hypothesis is that L-DOPA response, measured as an improvement in gait speed, is associated with a decrease in depressive symptoms and an increase in processing speed and working memory.

Start Date15 Aug 2024

Sponsor / Collaborator

University of British Columbia

[+1]

NCT06365515

/ RecruitingNot ApplicableIIT

Dopamine and Reward Learning Across Hormonal Transition Phases

Hormonal transition periods during the menstrual cycle may predispose women to mental disorders. Hormonal fluctuations provide specific neuroendocrine conditions that modulate brain structure and function and these actions affect cognitive and emotional behaviors and affect energy and mood homeostasis. It is thought that these changes are driven by altered dopamine transmission. Here, the investigators aim to examine (1) how sex hormones and dopamine are linked and also (2) how hormonal changes affect motivation, mood, and energy homeostasis.
To this end, dopamine intervention will be tested on effort-based decision-making and motivational circuits in three hormonal stages (i.e., women in early-follicular phase (EF), women in mid-luteal phase (ML), and men). Additionally, the effects of hormonal status on metabolic indices will be tested, and its effects on mood fluctuations in a period of a month.
The investigator hypothesizes that women in EF cycle phase (1) have naturally less dopamine and show less effort, and (2) they show greater improvement in effort-based decision-making after Levodopa administration. The investigator has exploratory outcomes about (3) sex differences in reward-learning with and without Levodopa administration and explores if these differences correlate with elevated female sex hormone levels. Moreover, it is hypothesized that (4) hormonal fluctuations affect energy homeostasis, thus women in their EF cycle phase have higher energy expenditure and (5) they report more negative mood than in their mid-luteal (ML) cycle phase.

Start Date01 May 2024

Sponsor / Collaborator

Deutsche Forschungsgemeinschaft

[+1]

JPRN-UMIN000054201

/ RecruitingNot Applicable

Low-dose L-DOPA treatment for drug-induced dystonia - Low-dose L-DOPA treatment for drug-induced dystonia

Start Date18 Apr 2024

Sponsor / Collaborator

Osaka Neurological Institute

100 Clinical Results associated with Levodopa hydrate

100 Translational Medicine associated with Levodopa hydrate

100 Patents (Medical) associated with Levodopa hydrate

38,057

Literatures (Medical) associated with Levodopa hydrate

01 Jun 2025·EXPERIMENTAL NEUROLOGY

Activating Wnt1/β-Catenin signaling pathway to restore Otx2 expression in the dopaminergic neurons of ventral midbrain

Article

Author: Zheng, Canbing ; Lin, Xian ; Ye, Tonglin ; Duan, Jinhai ; Gong, Zhuo ; Cao, AnQi ; Liu, Hao ; He, Yongqian ; Shen, Danyang ; He, Shuaiying ; Cen, Qikai ; Li, Zhao ; Zhu, Shunyan

Parkinson's disease (PD) is the world's second most prevalent neurodegenerative disease. Currently, aside from levodopa, there are no other effective drugs clinically available to slow its progression. Otx2 plays a critical role in the differentiation of midbrain dopaminergic neurons (mDANs) during midbrain development. However, in adulthood, Otx2 is primarily expressed in the ventral tegmental area (VTA)-ventral part, and mDANs in the dorsal part of the VTA and the substantia nigra pars compacta (SNc) show no Otx2 expression. Research indicates that Otx2 is essential not only for the development of mDANs but also for their protection against the toxicity of MPTP and rotenone. Consequently, Otx2 is a potential clinical target for mDANs protection. Identifying the upstream mechanism that regulates Otx2 expression is crucial to restoring its expression in the SNc and enhancing its levels in the entire ventral midbrain mDANs. In this study, we have demonstrated the safety of Otx2 overexpression in vitro by using adeno-associate virus (AAV) and explored the feasibility of promoting Otx2 expression through the Wnt/β-Catenin signaling pathway using various drugs, a miR-34 mimic, and an inhibitor. Our results showed that Otx2 overexpression via AAV in the SNc is relatively safe, and CHIR99021 can induce Otx2 expression in mouse mDANs, thereby, alleviating PD-liked motor symptoms induced by MPTP. These findings suggest that modulating Otx2 expression through the Wnt/β-Catenin signaling pathway holds a therapeutic approach for Parkinson's disease.

01 Jun 2025·BIOMATERIALS

Gelatin-DOPA-knob/fibrinogen hydrogel inspired by fibrin polymerization and mussel adhesion for rapid and robust hemostatic sealing

Article

Author: Yu, Lisha ; Ding, Yuan ; Liu, Zhaodi ; Wang, Weilin ; Ding, Yihang ; Mao, Zhengwei

Tissue adhesives have attracted significant interest in the field of hemostasis. However, challenges including weak tissue adhesion, inadequate biocompatibility, and instability limit their clinical applications. Here, we have developed a gelatin-DOPA-knob/fibrinogen hydrogel inspired by the fibrin polymerization and mussel adhesion, resulting in a biocompatible bioadhesive with outstanding adhesion performance and great storage stability. This strategy involves modifying gelatin with knob peptides and catechol groups inducing crosslinking with fibrinogen to form a hydrogel via knob-hole interactions, and enhancing interfacial adhesion performance by interacting with the blood-covered tissue through catechol groups and knob peptides. This hydrogel exhibits rapid gelation, enhanced mechanical strength and adhesion properties, compared to the commonly used fibrin glue in surgery. The hydrogel significantly reduces the time required to hemostasis and the amount of blood loss in severe hemorrhage models. It ensures superior hemostatic efficacy, excellent biocompatibility, and long-term storage stability, which holds significant promise in medical settings.

01 Jun 2025·Neural Regeneration Research

Role of the globus pallidus in motor and non-motor symptoms of Parkinson’s disease

Article

Author: Zhu, Huixian ; Qi, Zengxin ; Chen, Liang ; Jiang, Yimiao ; Yuan, Wangrui ; Shen, Kangli ; Liu, Ruiqi ; Lou, Weiwei ; Cao, Xin ; Fang, Chenxin ; Jiang, Yifan ; Zhuang, Qianxing

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson’s disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson’s disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson’s disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore, bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson’s disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson’s disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson’s disease, particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremor-dominant and non-tremor-dominant Parkinson’s disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity, and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson’s disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

458

News (Medical) associated with Levodopa hydrate

18 Mar 2025

·www.neurolixis.com

18 March 2025 - Neurolixis Publishes Positive Phase 2A Trial Results for NLX-112 in Parkinson’s Disease

Neurolixis today announced the publication of the results from its successful Phase 2A proof-of-concept clinical trial of NLX-112 (befiradol) in Parkinson’s disease. The findings, published in the prestigious journal 𝘔𝘰𝘷𝘦𝘮𝘦𝘯𝘵 𝘋𝘪𝘴𝘰𝘳𝘥𝘦𝘳𝘴, highlight NLX-112’s potential as a first-in-class, non-dopaminergic therapy with dual efficacy in addressing both levodopa-induced dyskinesia (LID) and motor impairment in Parkinson’s patients. The randomized, double-blind, placebo-controlled trial, supported by The Michael J. Fox Foundation and Parkinson’s UK, evaluated NLX-112 in patients with troubling LID. The study successfully met its primary endpoint of safety and tolerability, as well as its secondary endpoint of significantly reducing LID. Notably, NLX-112 also demonstrated anti-parkinsonian effects, significantly improving motor function in study participants. See the full publication (Open Access): 𝗡𝗟𝗫-𝟭𝟭𝟮 𝗿𝗮𝗻𝗱𝗼𝗺𝗶𝘇𝗲𝗱 𝗣𝗵𝟮𝗔 𝘁𝗿𝗶𝗮𝗹: 𝘀𝗮𝗳𝗲𝘁𝘆, 𝘁𝗼𝗹𝗲𝗿𝗮𝗯𝗶𝗹𝗶𝘁𝘆, 𝗮𝗻𝘁𝗶-𝗱𝘆𝘀𝗸𝗶𝗻𝗲𝘁𝗶𝗰 𝗮𝗻𝗱 𝗮𝗻𝘁𝗶-𝗽𝗮𝗿𝗸𝗶𝗻𝘀𝗼𝗻𝗶𝗮𝗻 𝗲𝗳𝗳𝗶𝗰𝗮𝗰𝘆. 𝘔𝘰𝘷𝘦𝘮𝘦𝘯𝘵 𝘋𝘪𝘴𝘰𝘳𝘥𝘦𝘳𝘴, 2025 (https://doi-org.libproxy1.nus.edu.sg/10.1002/mds.30175) 𝗔 𝗡𝗼𝘃𝗲𝗹 𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝗺 𝗼𝗳 𝗔𝗰𝘁𝗶𝗼𝗻: Unlike current Parkinson’s treatments that target the dopamine system, NLX-112 acts on the serotonin (5-HT) system, as a highly selective full activator of 5-HT1A receptors. This unique mechanism differentiates NLX-112 from previous serotonergic drugs and is believed to underlie its dual efficacy in reducing dyskinesia and improving motor function. The promising results from this Phase 2A trial support further development of NLX-112 as a transformative therapy for movement disorders. Neurolixis is actively planning next steps in the clinical development program to advance NLX-112 toward potential regulatory approval. 𝗔𝗯𝗼𝘂𝘁 𝗣𝗮𝗿𝗸𝗶𝗻𝘀𝗼𝗻’𝘀 𝗗𝗶𝘀𝗲𝗮𝘀𝗲 𝗮𝗻𝗱 𝗥𝗲𝗹𝗮𝘁𝗲𝗱 𝗠𝗼𝘃𝗲𝗺𝗲𝗻𝘁 𝗗𝗶𝘀𝗼𝗿𝗱𝗲𝗿𝘀: Parkinson’s disease is the second most common neurodegenerative disorder, affecting over 10 million people worldwide. Levodopa, the mainstay treatment for Parkinson’s, often leads to debilitating dyskinesias (involuntary movements) after prolonged use. Up to 80% of patients develop LID within ten years of levodopa therapy. Current treatments for LID, such as amantadine, are limited by side effects and variable efficacy, underscoring the need for new therapeutic options. As well as Parkinson’s disease, other disorders also involve dysfunction in the basal ganglia, a brain region critical for coordinating movement. Such disorders include spinocerebellar ataxia, Huntington’s disease, essential tremor and dystonia, and lead symptoms such as tremors, rigidity, and impaired motor control.

Phase 2Clinical Result

05 Mar 2025

·www.fiercebiotech.com

Celon\'s PDE10A inhibitor reduces involuntary movements in midstage Parkinson\'s trial

Celon Pharma said its therapy has a “unique pharmacodynamic profile, characterized by rapid enzyme dissociation, which distinguishes it from other PDE10A inhibitors.”\n Celon Pharma’s PDE10A inhibitor has reduced involuntary movements in a phase 2 trial of individuals with Parkinson’s disease.The Polish biotech tested two daily doses of the drug, dubbed CPL’36, in the study of 105 adults with Parkinson’s disease who had levodopa-induced dyskinesia (LID)—a term for involuntary movements caused by long-term use of the widely used Parkinson’s drug levodopa.By Week 4, the improvement in the Unified Dyskinesia Rating Scale was 12.3 units for patients who received the 20-mg dose and 13.58 units for those who received a 30-mg dose, hitting the trial’s primary endpoint.The study also hit “most” of its secondary endpoints, including a statistically significant difference in a related dyskinesia rating scale, the company added, without going into more details.No patients in the 20-mg cohort experienced severe adverse events, compared to 5.7% of the 40-mg group and 8.8% of patients who received placebo. A total of 11.1% of patients in the 20-mg dosing arm discontinued their medication due to treatment-related emergent adverse events, compared to 8.6% of the 40-mg cohort and 2.9% of the placebo group.“I am very pleased that the clinical effect of CPL\'36 has now been confirmed also for the treatment of LID dyskinesia in Parkinson\'s disease,” Celon’s CEO Maciej Wieczorek, Ph.D., said in a statement. “We believe that CPL’36 has potential to significantly contribute to the expansion and advancement of the global market for Parkinson\'s disease pharmacotherapy, and to provide sizeable clinical benefits to LID patients who are underserved by current treatments,” Wieczorek added.The post-market readout yesterday follows a “statistically significant” benefit demonstrated in a separate phase 2 trial in individuals with schizophrenia last year.Celon isn’t the only biotech trying to inhibit PDE10, an enzyme expressed in areas of the brain linked to a wide range of diseases that affect cognition. Swiss biotech Noema Pharma\'s gemlapodect—originally developed by Roche—reduced tic severity in a small phase 2 trial of 15 patients with Tourette syndrome last year. Meanwhile, EuMentis Therapeutics is aiming to take a PDE10A inhibitor into phase 2 in the first quarter of 2025, but it has failed to hit targets for the program in the past.Joanna Sierzputowska-Prarat, Celon’s main clinical neuropsychiatry lead, said in today’s release that CPL’36 has a “unique pharmacodynamic profile, characterized by rapid enzyme dissociation, which distinguishes it from other PDE10A inhibitors.”“We believe this attribute is key to the positive clinical outcomes we have generated thus far,\" Sierzputowska-Prarat added.

$Celon\'s PDE10A inhibitor reduces involuntary movements in midstage Parkinson\'s trial$

Phase 2Clinical Result

06 Feb 2025

·www.pharmaceutical-technology.com

Supernus wins FDA approval for Parkinson’s pump on fourth try

Onapgo is approved for adult Parkinson’s patients experiencing motor fluctuations. Credit: Inside Creative House via Getty Images. Supernus Pharmaceuticals has won US approval for its wearable pump Onapgo (apomorphine hydrochloride) to treat symptoms of Parkinson’s disease. Supernus’ regulatory path for Onapgo has been marked by multiple setbacks over nearly five years, with the Food and Drug Administration (FDA) rejecting three prior applications before securing approval. The company acquired Onapgo, previously known as SPN-830, from US WorldMeds in 2020. Soon after, Supernus submitted its first application for FDA review. However, in 2020, the agency issued a refusal-to-file (RTF) letter, determining that the submission was incomplete and not ready for formal review. Supernus resubmitted the application twice, receiving complete response letters (CRLs) both times. The first 2022 rejection required further analysis of the infusion device and drug product, while the most recent CRL, issued in April 2023, cited product quality concerns and deficiencies in the master file for the proprietary pump. The company resubmitted its fourth application in August, leading to the current approval. Onapgo will now be available for adult Parkinson’s disease patients experiencing motor fluctuations. The wearable pump is designed to provide a continuous subcutaneous infusion of Supernus’ apomorphine (Apokyn). The drug is intended for patients experiencing “off” periods, where medication wears off and symptoms return or worsen. The approval is based on a Phase III, 12-week study (NCT02006121) involving 107 patients. Onapgo led to a drop in daily “off” time and an increase in daily good “on” time, defined as periods without dyskinesia and the patient’s global impression of change (PGIC). Supernus plans to launch Onapgo in the second quarter of 2025, supported by a team of specialists, a nurse education programme, and access support services. The approval adds Onapgo to a growing list of infusion-based Parkinson’s treatments. AbbVie ’s Vyalev (foscarbidopa and foslevodopa), a continuous subcutaneous infusion therapy combining prodrugs of carbidopa and levodopa, was approved in October 2024 after three regulatory attempts. The FDA’s initial rejection of Vyalev did not involve efficacy or safety concerns but requested additional information on the pump device. The second rejection followed findings of issues at a third-party manufacturer. AbbVie set a precedent in 2015 with its Parkinson’s disease infusion pump therapy Produodopa (foslevodopa foscarbidopa), sparking innovation in drug delivery systems as companies looked for alternatives for conventional oral treatments.

Drug ApprovalPhase 3

100 Deals associated with Levodopa hydrate

External Link

KEGG	Wiki	ATC	Drug Bank
D00059	Levodopa hydrate	N04BA01	DB01235

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Parkinson Disease	United States	Hoffmann-La Roche, Inc.	04 Jun 1970
Parkinson Disease	United States	Shire Development LLC	04 Jun 1970

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Dyskinesias	Phase 3	United States	AbbVie, Inc.	01 Jun 2009
Dyskinesias	Phase 3	Germany	AbbVie, Inc.	01 Jun 2009
Dyskinesias	Phase 3	New Zealand	AbbVie, Inc.	01 Jun 2009
Asthma	Phase 1	United States	Acorda Therapeutics, Inc.	01 Dec 2015
Smoking	Phase 1	United States	Acorda Therapeutics, Inc.	01 Dec 2015

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


EAN2024	Not Applicable	Parkinson Disease	-	Inhaled levodopa	hftwokccuh(yprxvtpgct) = reported by 12 (66.7%) patients fwxktagozv (bbsbuagrfu ) View more	-	28 Jun 2024
S2.007 (AAN2024)	Not Applicable	Activated PI3K-delta Syndrome	-	Carbidopa-levodopa enteral suspension (CLES)	nmiaqfkxgt(flikelmoeh) = zlrttaivok wdtkuilvhz (aithsopzip )	Negative	09 Apr 2024
				Surgical Device-aided Therapies (DATs) (Deep brain stimulation (DBS))	nmiaqfkxgt(flikelmoeh) = tloozsapza wdtkuilvhz (aithsopzip )
MDS2023	Not Applicable	-	110	LD/DCI	nndgwuntai(iqxjrackhr) = rqudedxrvw qrmgsyrsva (nybfcztweh ) View more	Positive	27 Aug 2023
				LD/DCI+COMT-I	nndgwuntai(iqxjrackhr) = cawmmmsdos qrmgsyrsva (nybfcztweh ) View more
MDS2023	Not Applicable	Parkinson Disease	-	Levodopa/Benserazide	fdosyiimmn(gjlnqtrzox) = avblptwqnw cleculiydj (synyefaywh )	Negative	27 Aug 2023
				Placebo	fdosyiimmn(gjlnqtrzox) = jbpfrhmzng cleculiydj (synyefaywh )
MDS2023	Not Applicable	Parkinson Disease calpains	16	Without levodopa	zxiyrsrrvh(klrfdlmpnf) = lsbhbdobra lqdwffvwai (jcsecpmymg, - 0.11)	Positive	27 Aug 2023
				Daily dose up to 600 mg	zxiyrsrrvh(klrfdlmpnf) = zoyqcbckrk lqdwffvwai (jcsecpmymg, - 0.16)
MDS2023	Not Applicable	Parkinson Disease	-	levodopa	zcegbsctnm(tnyzuwvoiv) = llphuzbhoy bkjkxxfsjj (jmjynkrbhl )	Positive	27 Aug 2023
				levodopa	luigucxidw(lbgijwrfxw) = qmjanywbvm hfibigorgy (likdtbotlc ) View more
MDS2023	Not Applicable	Dystonic Disorders	-	Pre-levodopa administration	swsqtgtasa(hhavogauns) = nnfxfxcrbg folmnbrsvf (dpfytierbe )	-	27 Aug 2023
				Post-levodopa administration	swsqtgtasa(hhavogauns) = rytatujgee folmnbrsvf (dpfytierbe )
MDS2023	Not Applicable	Parkinson Disease	3	Levodopa intake	wkvnwtpmyv(vqnlhealco) = htcmfovvam mazsgeugvg (oyhzrkhvuh, 57.2)	Positive	27 Aug 2023
PD MED early disease randomisation (MDS2023)	Not Applicable	Parkinson Disease	1,593	Levodopa-sparing therapy (dopamine agonist or monoamine oxidase B inhibitor)	hdgiptcjwz(gkhpzcwxyf): P-Value = 0.84 View more	Positive	27 Aug 2023
				Levodopa alone

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