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

University Hospital Tuebingen

[+2]

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

39,776

Literatures (Medical) associated with Levodopa hydrate

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 ; Fang, Chenxin ; Cao, Xin ; 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.

01 Apr 2025·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

A reliable LC-MS/MS method for the quantification of natural amino acids in human plasma and its application in clinic

Article

Author: Lin, Junhuan ; Li, Li ; He, Debo ; Zhang, Yangrui ; Ou, Fengting ; Ke, Tao ; Yu, Lushan ; Song, Yibo ; Zeng, Kui

A simple and fast LC-MS/MS method was developed and validated for simultaneous quantification of 20 L-amino acids (AAs) in human plasma. Chromatographic separation was achieved on an Agilent AdvanceBio Hilic column within 15 min via gradient elution with an aqueous solution containing 5 mM ammonium formate, 5 mM ammonium acetate and 0.1 % formic acid and an organic mobile phase containing 0.1 % formic acid, 5 mM ammonium formate and 5 mM ammonium acetate acetonitrile-water (90:10, v/v) at the flow rate of 0.25 mL/min. Individual AAs and internal standard were analyzed by multiple reaction monitoring (MRM) in positive ion mode under optimized conditions. Method validation consisted of linearity, sensitivity, accuracy and precision, recovery, matrix effect, and stability, and the results demonstrated this LC-MS/MS method as a specific, accurate, and reliable assay. The method was thus utilized to compare the dynamics of individual plasma AAs between healthy females and patients with ovarian tumors. Our results revealed that, in cancer group, plasma 3-Methyl-L-Histidine, L-Proline, L-Phenylalanine and L-Lysine concentrations were significantly increased in patients with malignant ovarian tumors while L-Leucine and L-Isoleucine levels were sharply decreased. These findings support the utilities of this LC-MS/MS method and the promise of specific AAs as possible biomarkers for ovarian cancer.

01 Apr 2025·Neural Regeneration Research

Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Article

Author: Bi, Yuewei ; Wang, Pengfei ; Zhou, Ming ; Wen, Huantao ; Li, Min ; Wang, Zhuyong ; Chen, Jiazhi ; Luo, Minjie ; Zhang, Wangming

JOURNAL/nrgr/04.03/01300535-202504000-00031/figure1/v/2024-07-06T104127Z/r/image-tiff Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

385

News (Medical) associated with Levodopa hydrate

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

04 Feb 2025

·endpts.com

FDA approves Supernus’ Parkinson’s drug-device after two rejections

At long last, the FDA approved Supernus Pharmaceuticals’ Parkinson’s disease treatment, which will be marketed as Onapgo. Onapgo is now approved to treat motor fluctuations in adults with advanced Parkinson’s disease. Previously known as SPN-830, the therapy is administered using a pump that continuously delivers apomorphine, a drug used to treat what’s known as “off” episodes in Parkinson’s disease. That’s when Parkinson’s symptoms, like stiffness or tremors, affect patients between doses of medication such as levodopa. In a Phase 3 study, Onapgo reduced the amount of daily “off” time by 2.6 hours compared to 0.9 hours with placebo at 12 weeks. Supernus said Onapgo will be available in the US in the second quarter of this year. Supernus declined to disclose the price for Onapgo, saying it isn’t commenting on pricing before the product is commercially available. Its stock $SUPN was up about 5% on Tuesday morning. The regulator’s approval occurred less than a year after it rejected the treatment for the second time in April. At that time, the FDA said it needed additional information or review time for two items: product quality, and the “master file” for the device part. In 2022, the agency also rejected the drug-device, and in 2020, the FDA refused to review Supernus’ application for SPN-830. Other companies have or are developing similar therapies. AbbVie in October received FDA approval for Vyalev, which is a continuous infusion used to treat Parkinson’s. And Mitsubishi Tanabe Pharma is working to resubmit an application to the FDA for its continuous infusion pump ND0612 after it was rejected. Supernus acquired the program in 2020 as part of its $300 million purchase of US WorldMeds’ CNS portfolio. Supernus is also the maker of the ADHD drug Qelbree, among other drugs for psychiatric and neurologic conditions. Editor’s note: This story was updated with Supernus’ comment on pricing.

Clinical ResultDrug ApprovalAcquisitionPhase 3

04 Feb 2025

·medcitynews.com

Supernus Wearable Device for Dosing Parkinson’s Drug Lands Long-Awaited FDA Approval - MedCity News

A new Supernus Pharmaceuticals medical device that continuously administers an old Parkinson’s disease drug is now FDA approved, giving patients another way to manage the motor control symptoms that return when the effects of standard treatment for the neurological disease wanes. The drug/device combination product, known in development as SPN-830, will be commercialized under the brand name Onapgo. Supernus said Tuesday it plans to launch Onapgo in the second quarter of this year. In an email, the Rockville, Maryland-based company, which specializes in treatments for central nervous system diseases, said it cannot comment on pricing of products before they become commercially available. The backbone of Parkinson’s treatment is levodopa, a compound that is converted to dopamine in the brain to boost levels of this brain chemical that patients lack. The periods when this medication works are called “on” times. But Parkinson’s patients also experience “off” times when levodopa therapy wears off and motor symptoms return. One treatment option for these off periods is a different drug, apomorphine. presented by sponsored content, Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum Apomorphine mimics dopamine, binding to receptors responsible for motor control. An FDA-approved injectable version of this drug has been available for more than 20 years for treating the off episodes of Parkinson’s. In 2020, Sunovion Pharmaceuticals’ sublingual film formulation of apomorphine received FDA approval for intermittent treatment of the off episodes of Parkinson’s. Supernus already has a presence in Parkinson’s. Its second-largest product by revenue is Gocovri, a capsule that treats dyskinesia and off time in Parkinson’s patients. The company also already markets apomorphine, dosed as needed via an injection pen product branded as Apokyn. But motor symptoms of Parkinson’s worsen as the disease progresses and off periods can happen at any time. Continuous infusion of apomorphine offers an additional way to manage these unpredictable off times. Supernus sources Apokyn from Britannia Pharmaceuticals, a subsidiary of German company Stada Arzneimittel. Britannia markets both injectable and continuous infusion apomorphine products in Europe. A license and supply agreement with Britannia grants Supernus the right to use and market injectable apomorphine in the U.S. The 2016 pact also covers the joint development of other apomorphine products, including drug administered as a continuous infusion. Supernus must pay Britannia royalties on net sales for products covered by the agreement. Britannia retains rights to its drug outside of the U.S. Onapgo, a device secured to the body by an elastic band worn around the waist, has had a rocky regulatory journey leading up to its FDA nod. Supernus applications seeking regulatory approval were turned back by the FDA in 2022 and again last April, as the agency asked for more information about various aspects of the drug/device combination product candidate. Last August, the FDA accepted Supernus’s resubmitted application and set a Feb. 1 target date for a regulatory decision. presented by Health IT Transforming Patient Care: The Role of AI-Powered Assistants The progress in artificial intelligence (AI) is reshaping patient care, across various dimensions, from facilitating faster discharge to curating treatment plans and suggesting lifestyle changes. By IT Medical The long-awaited FDA approval is based on the results of a placebo-controlled Phase 3 test that evaluated Onapgo for 12 weeks. Results showed that patients who received the Supernus treatment experienced a 2.6-hour reduction in daily off time compared to 0.9 hours for those who received a placebo. Patients who received the Supernus treatment also experienced an increase in on time for their Parkinson’s medications — 2.8 hours for the Onapgo arm compared to 1.1 hours for the placebo group. The most common adverse events reported in the study included infusion-site reactions, nausea, sleepiness, dyskinesia, headache, and insomnia. In Supernus’s announcement of the product approval, Dr. Rajesh Pahwa noted the 30-year history of continuous subcutaneous apomorphine infusions in Europe. Pahwa, a professor of neurology at the University of Kansas School of Medicine, director of the Movement Disorder Program at The University of Kansas Health System, and an investigator for Onapgo’s clinical trial, pointed to the significant reduction in off time and increase in on time for patients treated with the Supernus product. “Today’s approval of Onapgo means patients in the U.S. who are not responding well to their current treatment regimen, including levodopa, will now have the option of using a small and lightweight wearable device to deliver a continuous infusion without the need for an invasive surgical procedure,” Pahwa said. Photo by Supernus Pharmaceuticals

Clinical ResultDrug ApprovalPhase 3License out/in

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	US	Hoffmann-La Roche, Inc.	04 Jun 1970
Parkinson Disease	US	Shire Development LLC	04 Jun 1970

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dyskinesias	Phase 3	US	AbbVie, Inc.	01 Jun 2009
Dyskinesias	Phase 3	DE	AbbVie, Inc.	01 Jun 2009
Dyskinesias	Phase 3	NZ	AbbVie, Inc.	01 Jun 2009
Asthma	Phase 1	US	Acorda Therapeutics, Inc.	01 Dec 2015
Smoking	Phase 1	US	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	qbsnxekufm(hilauccztx) = reported by 12 (66.7%) patients pemlwhigdk (abqqvcvqnl ) View more	-	28 Jun 2024
S2.007 (AAN2024)	Not Applicable	Activated PI3K-delta Syndrome	-	Carbidopa-levodopa enteral suspension (CLES)	qmsdzxqywf(ihlxtxzyfr) = oykolwzymr npukrdtmiq (wdwfafqodt )	Negative	09 Apr 2024
				Surgical Device-aided Therapies (DATs) (Deep brain stimulation (DBS))	qmsdzxqywf(ihlxtxzyfr) = sucbkxdzem npukrdtmiq (wdwfafqodt )
INVEST study (MDS2023)	Not Applicable	Parkinson Disease	-	Continuous intrajejunal levodopa infusion (CILI)	vxggbugplf(tghdptzfgc) = gxhjincnks pfawjzsytn (gjlyzpvrsp, -2.9 to 11.0)	-	27 Aug 2023
MDS2023	Not Applicable	Parkinson Disease	-	levodopa	bnqtoiejrj(pqipjdpsyf) = wrctjoxbbf uoimfxzovh (dqqzkxycdm )	Positive	27 Aug 2023
				levodopa	gdnznbsbzj(naewtilcln) = oiolkhunsy ehjsjtjoge (webqecqebp ) View more
MDS2023	Not Applicable	Dystonic Disorders	-	Pre-levodopa administration	rlqoegtirr(ohfuthdsni) = hfgdkknjyb vufncrorqa (bweptdbwqm )	-	27 Aug 2023
				Post-levodopa administration	rlqoegtirr(ohfuthdsni) = ilzloepcrb vufncrorqa (bweptdbwqm )
PD MED early disease randomisation (MDS2023)	Not Applicable	Parkinson Disease	1,593	Levodopa-sparing therapy (dopamine agonist or monoamine oxidase B inhibitor)	qedbfmlgxp(udlzhyizgy): P-Value = 0.84 View more	Positive	27 Aug 2023
				Levodopa alone
Parkinson’s Progression Markers Initiative (PPMI) (MDS2023)	Not Applicable	Parkinson Disease	428	levodopa	mmnksbfzmv(huquqohjeg) = izpserxzlm fnguuszavl (txepiwqgza )	-	27 Aug 2023
				levodopa	mmnksbfzmv(huquqohjeg) = tytfwidmqe fnguuszavl (txepiwqgza )
MDS2023	Not Applicable	-	110	LD/DCI	mgswrjggey(tikxwmxzee) = vigdgeaxmk nunknqweee (vnsipzznys ) View more	Positive	27 Aug 2023
				LD/DCI+COMT-I	mgswrjggey(tikxwmxzee) = bxoeeolbvu nunknqweee (vnsipzznys ) View more
MDS2023	Not Applicable	Parkinson Disease calpains	16	Without levodopa	dilvqnaojp(qywoxnakww) = sefjabpdoo yujrchscyo (nzpmwcoyuw, - 0.11)	Positive	27 Aug 2023
				Daily dose up to 600 mg	dilvqnaojp(qywoxnakww) = djldwnrnge yujrchscyo (nzpmwcoyuw, - 0.16)

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