The Comparative Pilot Bioavailability Study of a Generic Test Formulation of Selegiline TDS 6 mg/24 Hours Against the Comparator EMSAM® 6 mg/24 Hours in Healthy Adult Subjects

The goal of this clinical study is to obtain the bioavailability of the test patch of a generic formulation of Selegiline TDS 6mg/24 hours by Corium Innovations against the comparator (EMSAM), and the systemic and local safety and tolerability will be also observed and evaluated.

Start Date15 Oct 2024

Sponsor / Collaborator

Corium Innovations, Inc.

DRKS00023352 / CompletedPhase 1IIT

Pharmacokinetic profile of betahistine blood concentration with and without selegiline in healthy volunteers - a mono-center, open-labeled phase I trial - PK-BeST

Start Date08 Jun 2021

Sponsor / Collaborator-

IRCT20200719048136N1 / RecruitingPhase 2/3IIT

The effect of selegiline on functional and cognitive recovery in stroke patients

Start Date22 Aug 2020

Sponsor / Collaborator-

100 Clinical Results associated with Selegiline

100 Translational Medicine associated with Selegiline

100 Patents (Medical) associated with Selegiline

1,449

Literatures (Medical) associated with Selegiline

24 Oct 2024·Current Medicinal Chemistry

Design, Synthesis, Molecular Docking, Pharmacokinetic Properties, and Molecular Dynamics Simulation of Sulfonyl Derivatives of Benzimidazole against Parkinson’s Disease

Article

Author: Biswas, Goutam ; Barman, Hema ; Sen, Subhadeep ; Roy, Subarna ; Roy, Shristi ; Das, Rajesh Kumar ; Dey, Paromita ; Basak, Subhankar ; Debnath, Sudhan ; Sarkar, Kaushik ; Singh, Bhagat

Introduction:The disability and mortality related to Parkinson's disease (PD), a neurodegenerative disease, are increasing globally at a faster rate than other neurological disorders. With no permanent cure for PD, there is an urgent need to develop novel and effective anti-PD drugs.Method:Targeting monoamine oxidases (MAO), which catalyze the breakdown of neurotransmitters, is one way to treat neurodegenerative diseases. In this context, an initial molecular docking of twenty designed sulfonyl derivatives of benzimidazole against monoamine oxidase B (MAO-B) associated with PD was conducted using AutoDock Vina.Result:The results were compared with those of the conventional inhibitors, selegiline and rasagiline. Based on the docking score, the in-silico pharmacokinetic properties (ADME), drug-likeness, and toxicity profiles of the newly synthesized molecules were examined using SwissADME, PreADMET, ProTox-3.0, vNN, and ADMETlab web tools. Then, twelve potential derivatives were synthesized and characterized by IR, 1H-NMR, 13C-NMR, 19F-NMR (for some compounds), and mass spectrometry. Derivatives 2cj and 1bj were the two molecules having the best binding affinity of -11.9 and -11.8 kcal/mol, respectively, against MAOB, exhibiting a higher binding affinity compared to that of some commercially available drugs. A 50 ns MD simulation run was performed to observe the stability of the top two docked complexes, MAO-B-2cj and MAO-B-1bj, in order to further validate the efficacy of those two substances. Moreover, the MM-PBSA method was used to calculate the final, binding free energy of the simulated (MAO-B-2cj) complex.Conclusion:This study indicates that the binding affinity of most of the hits was superior to that of known MAO inhibitors; therefore, these newly synthesized benzimidazole derivatives may be developed into essential drug candidates for the treatment of PD.

23 Oct 2024·Current Medicinal Chemistry

Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A Comprehensive In Silico, In Vitro, and In Vivo Studies on its Neuroprotective Effects and Molecular Interactions in Parkinson's Disease

Article

Author: Yazdanpanah, Mohammad Ali ; Simorgh, Sara ; Amiri, Mobina ; Azedi, Fereshteh ; Kokabi, Shayesteh ; Barati, Mahmood ; Shahbazi, Ali ; Angaji, Seyed Abdolhamid ; Tavakol, Shima ; Alahdad, Niloofar

Introduction:Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic cells and as of now, there is no established definitive treatment available for this condition.Method:In this study, the focus was on investigating the impact of SVAK-12, a small molecule that can cross the blood-brain barrier and remain stable without structural changes. The effect of SVAK-12 was investigated in vitro on neurotoxicity, in vivo model of Parkinson's Diseases and in silico.Result:Through in vitro and in vivo experiments, as well as molecular docking simulations, it was found that SVAK-12 (375 ng.ml) led to increased cell viability, reduced cellular damage, and decreased production of NO and ROS. Additionally, it boosted levels of important neurotrophic factors like BDNF (130.49%) and GDNF (116.38%), potentially aiding in alleviating motor disability and depression. The study also highlighted SVAK-12's potential as a therapeutic candidate for neurological disorders due to its ability to increase tyrosine hydroxylase expression and dopamine levels (4.84 times). While it did not significantly improve motor symptoms in vivo, it did enhance motor asymmetry in the forelimbs and gene expression related to brain regions. Besides, it induced significant BMP-2 gene expression in substantial nigra regions without significant changes in GDNF and Nurr1 gene expression in the striatum expression. The docking of SVAK-12, Levodopa, Amantadine, Biperiden, Selegiline, and Rasagiline to the binding site of GFRα1, sortilin, and TrkB showed that SVAK-12 had greater MolDock score than Selegiline and Amantadine for GFRα1 and greater than amantadine for Sortilin and TrKB.Conclusion:Overall, the study suggests that SVAK-12's neuro-biocompatibility, ability to reduce free radicals, and enhanced neurotrophic factors make it a promising candidate as a neuroprotective drug.

01 Oct 2024·Current Computer-Aided Drug Design

Molecular Mechanism and Structure-activity Relationship of the Inhibition Effect between Monoamine Oxidase and Selegiline Analogues

Article

Author: Gao, Chang ; Wang, Haoce ; Wang, Xiaoning ; Liu, Yonglin ; Liu, Yunxiang ; Zang, Jinqiu ; Yang, Chuanxi ; Wang, Weiliang ; Liu, Lin ; Ma, Ziyi ; Sun, Haofen

Introduction:To investigate the inhibition properties and structure-activity relationship between monoamine oxidase (MAO) and selected monoamine oxidase inhibitors (MAOIs, including selegiline, rasagiline and clorgiline).Methods:The inhibition effect and molecular mechanism between MAO and MAOIs were identified via the half maximal inhibitory concentration (IC50) and molecular docking technology.Results:It was indicated that selegiline and rasagiline were MAO B inhibitors, but clorgiline was MAO-A inhibitor based on the selectivity index (SI) of MAOIs (0.000264, 0.0197 and 14607.143 for selegiline, rasagiline and clorgiline, respectively). The high-frequency amino acid residues of the MAOIs and MAO were Ser24, Arg51, Tyr69 and Tyr407 for MAO-A and Arg42 and Tyr435 for MAO B. The MAOIs and MAO A/B pharmacophores included the aromatic core, hydrogen bond acceptor, hydrogen bond donor-acceptor and hydrophobic core.Conclusion:This study shows the inhibition effect and molecular mechanism between MAO and MAOIs and provides valuable findings on the design and treatment of Alzheimer's and Parkinson's diseases.

News (Medical) associated with Selegiline

09 Jan 2024

·www.prnewswire.com

AbbVie Launches PRODUODOPA® (foslevodopa/foscarbidopa) for People Living with Advanced Parkinson's Disease in the European Union

- PRODUODOPA® (foslevodopa/foscarbidopa) is the first-and-only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of advanced Parkinson's disease - PRODUODOPA demonstrated sustained improvements in "Off" time (when symptoms return between medication doses), "On" time (when symptoms are controlled) without dyskinesia (involuntary movement), and morning akinesia ("Off" time upon waking) NORTH CHICAGO, Ill., Jan. 9, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the launch of PRODUODOPA® (foslevodopa/foscarbidopa) in the European Union for the treatment of advanced Parkinson's disease with severe motor fluctuations and hyperkinesia (excessive movement) or dyskinesia (involuntary movement), and when available combinations of Parkinson's medicinal products have not given satisfactory results.1 PRODUODOPA is the first-and-only subcutaneous 24-hour infusion of levodopa-based therapy for the treatment of severe motor fluctuations in people living with advanced Parkinson's disease whose symptoms are inadequately controlled by other therapies. The continuous delivery of PRODUODOPA provides levodopa 24-hours a day which may help patients by extending the period when symptoms are well-controlled, often referred to as "On" time.2 AbbVie was granted marketing authorization of PRODUODOPA through the Decentralized Procedure in the third quarter of 2022. The VYAFUSER™ pump for the subcutaneous delivery of PRODUODOPA received Conformité Européenne (CE) Mark in November of 2023. Parkinson's disease is a chronic, progressive neurodegenerative disorder affecting approximately 6.1 million people globally3 and is expected to double by 2040. Parkinson's disease is characterized by tremor, muscle rigidity, slowness of movement and difficulty with balance.4 As the disease progresses, the severity of symptoms increases5, and patients tend to experience greater disability and an impaired ability to perform activities of daily living6, as well as the reemergence of symptoms as standard treatment wears off.7 Characteristics of advanced Parkinson's disease may include needing help with performing daily activities, increased motor fluctuations (changes in the ability to move referred to as "On-Off" times), difficulty swallowing, recurrent falls, dementia, dyskinesia (involuntary movements) and other symptoms.5 "People living with Parkinson's disease experience daily challenges and uncertainty, especially as their disease progresses and symptoms are no longer adequately controlled," said Roopal Thakkar, Senior Vice President, Development and Regulatory Affairs and Chief Medical Officer, AbbVie. "This approval is an example of our unwavering commitment to this community by developing new, transformative therapeutic options for people experiencing advanced Parkinson's disease, their families, and care partners." The launch was supported by three studies: the Phase 3, 12-month open label study (M15-741 study) which evaluated the long-term safety, tolerability, and efficacy of continuous subcutaneous infusion of PRODUODOPA8, the Phase 3, 12-week study (M15-736 study) which compared the efficacy and safety of PRODUODOPA to oral levodopa/carbidopa2, and a Phase 1 pharmacokinetic comparability study.9 Findings from the M15-741 safety and tolerability study showed a favorable benefit/risk profile and demonstrated sustained improvements in "Off" time and "On" time without dyskinesia, and morning akinesia as measured by the percentage of patients in early morning "Off" time as recorded by PD diary.8 The majority of adverse events (AEs) with PRODUODOPA were non-serious and mild or moderate in severity. The most frequent AEs (greater than or equal to 10 percent) were infusion site events (infusion site erythema, infusion site cellulitis, infusion site nodule, infusion site pain, infusion site oedema, infusion site reaction, and infusion site infection), hallucination, fall, and anxiety.1 "This approval represents a significant advancement for those with Parkinson's disease who have historically had limited treatment options for advanced stages," said Angelo Antonini, MD, PhD, Professor of Neurology at the Department of Neuroscience, University of Padua, Italy. "When oral treatment no longer sufficiently helps with improvement in motor fluctuations, patients need alternative options. PRODUODOPA's around-the-clock infusion allows for continuous delivery of levodopa, the gold standard of treatment." "As Parkinson's progresses, it can take a significant physical and emotional toll not only on the person but also on their family and care partners, who often play a critical role in their daily lives," said Josefa Domingos, President, Parkinson's Europe. "It is vital that the Parkinson's community have more options that can help them manage their symptoms." About the Phase 3 M15-741 Study8 The Phase 3, single arm, open-label study evaluated the safety and tolerability, and efficacy of 24-hour daily exposure of continuous subcutaneous infusion of PRODUODOPA in people with advanced Parkinson's disease whose motor symptoms were inadequately controlled by their current treatment. The primary endpoint was to evaluate the safety and tolerability of PRODUODOPA. Secondary endpoints included changes from baseline in normalized "Off" and "On" time, percentage of patients reporting morning akinesia, and total scores from quality-of-life surveys. The study was conducted at 58 sites across 13 countries (Australia, Belgium, Canada, Denmark, Germany, Italy, Japan, Netherlands, Russia, Spain, Sweden, United Kingdom, and United States). Eligible patients included adults 30 years or older diagnosed with levodopa-responsive idiopathic Parkinson's disease experiencing an average of greater than or equal to 2.5 hours of "Off" time per day, as assessed by patient's Parkinson's disease diaries. Reduction in motor fluctuations was observed as early as one week and persisted through week 52. The percentage of patients experiencing morning akinesia dropped from 77.7 percent at baseline to 27.8 percent at week 52. Indicators of sleep and quality of life were assessed from baseline through week 52 as published in the Journal of Neurology & Therapy (). More information on the study can be found on (NCT03781167). About the Phase 3 M15-736 Study2 The Phase 3 randomized, double-blind, double-dummy, active-controlled study compared the efficacy, safety and tolerability of PRODUODOPA to oral immediate-release levodopa/carbidopa (LD/CD) in patients with advanced Parkinson's disease. Participants were provided with a home diary (the PD Diary) to assess their motor state during the day. The primary endpoint was "On" time without troublesome dyskinesia. The study included 141 participants who were randomly assigned and received treatment at 65 centers in the U.S. and Australia. Participants were randomized one to one to receive either the PRODUODOPA solution as a continuous delivery under the skin (subcutaneous) plus oral placebo capsules for LD/CD or oral capsules containing immediate-release LD/CD plus continuous subcutaneous delivery of placebo solution for PRODUODOPA. The treatment duration was 12 weeks. The increase in "On" time without troublesome dyskinesia at week 12 was an average of 2.72 hours for PRODUODOPA versus 0.97 hours for oral LD/CD (p= 0.0083). Improvements in "On" time were observed as early as the first week and persisted throughout the 12 weeks. This study also assessed changes from baseline to week 12 in motor experiences of daily living, morning akinesia, sleep, and quality of life indicators, however results did not achieve statistical significance. More information on the study can be found on (NCT04380142) and in The Lancet Neurology ((22)00400-8). About the Phase 1 Pharmacokinetic study9 A Phase 1, open label, randomized, two period cross over study was conducted to compare the pharmacokinetics (PK) of levodopa from 24-hour continuous subcutaneous infusion of PRODUODOPA (foslevodopa/foscarbidopa) to the PK of levodopa from 16-hour levodopa-carbidopa intestinal gel (LCIG), followed by two night-time oral levodopa/carbidopa (LD/CD) doses. The levodopa exposures following subcutaneous infusion of PRODUODOPA over 24 hours were similar (less than 8 percent difference) to those of LCIG mg LD/CD administered over 16 hours, followed by two oral doses at 18 and 21 hours after the start of LCIG delivery. The study concluded that 24-hour continuous subcutaneous infusion of PRODUODOPA provides levodopa exposures comparable to LCIG throughout the day. More information on the study can be found on (35339102) and in Science Direct (). About PRODUODOPA® (foslevodopa/foscarbidopa) PRODUODOPA® (foslevodopa/foscarbidopa) is a solution of levodopa and carbidopa prodrugs for 24-hour continuous subcutaneous infusion for the treatment of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results. PRODUODOPA® (foslevodopa and foscarbidopa solution for infusion) Indication and Summary of Important Treatment Considerations1 Indication Treatment of advanced levodopa-responsive Parkinson's disease with severe motor fluctuations and hyperkinesia or dyskinesia when available combinations of Parkinson medicinal products have not given satisfactory results. Contraindications PRODUODOPA is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients, narrow-angle glaucoma, severe heart failure, acute stroke, severe cardiac arrhythmia, co-medication with selective MAO type A inhibitors and nonselective MAO inhibitors, conditions contraindicated for adrenergics (e.g. pheochromocytoma, hyperthyroidism, and Cushing's syndrome), and suspicious undiagnosed skin lesions or history of melanoma. Select special warnings and precautions for PRODUODOPA Special warnings and precautions for PRODUODOPA Several warnings and precautions below are generic for levodopa and, therefore, also for PRODUODOPA. Not recommended for the treatment of drug-induced extrapyramidal reactions. Caution use in patients with: severe cardiovascular or pulmonary disease, bronchial asthma, renal, hepatic or endocrine disease, or history of peptic ulcer disease or of convulsions. History of myocardial infarction with residual atrial nodal or ventricular arrhythmias, cardiac function should be monitored during the initial dosage adjustments. Monitor all patients for the development of mental changes, depression with suicidal tendencies, and other serious mental changes. Caution with past or current psychosis and antipsychotics used concomitantly with dopamine receptor-blocking properties (observe for loss of antiparkinsonian effect). Higher frequency of hallucinations may occur with dopamine agonists and/or other dopaminergic treatments including PRODUODOPA. Monitor patients regularly for the development of impulse control disorders, for example Dopamine Dysregulation Syndrome (DDS). Before initiation of treatment, warn patients and caregivers of the potential risk of developing DDS. The dose of PRODUODOPA may need to be adjusted downwards in order to avoid levodopa induced dyskinesias. Caution in chronic wide-angle glaucoma; monitor for intra-ocular pressure changes. PRODUODOPA may induce orthostatic hypotension and should be given cautiously in patients taking other medicinal products that may cause orthostatic hypotension. Concomitant use of selegiline and levodopa/carbidopa has been associated with serious orthostatic hypotension. Levodopa may induce somnolence and sudden sleep: caution should be exercised when driving and operating machines. Risk of symptoms resembling Neuroleptic Malignant Syndrome following abrupt dose reduction or discontinuation. Infusion site events (see section 4.8) have been reported in patients receiving PRODUODOPA. Follow aseptic techniques and frequently rotate the infusion site to reduce the risk. In clinical studies, few patients who reported infusion site reactions also experienced infusion site infections. Therefore, monitor for serious infusion site reactions and infusion site infections. Patients with Parkinson's disease have a higher risk of developing melanoma. Monitor patients for melanomas on a regular basis when using PRODUODOPA. Periodic evaluation of hepatic, haematopoietic, cardiovascular and renal function is recommended during extended therapy with PRODUODOPA. PRODUODOPA contains hydrazine (foscarbidopa degradation product), that can be genotoxic and probably carcinogenic. The approximately median exposure of hydrazine is 0.2 mg/day, with a maximum of 0.5 mg/day. The clinical significance of this hydrazine exposure is not known. Reduced ability to handle the delivery system can lead to complications. In such patients a caregiver should assist the patient. A sudden or gradual worsening of bradykinesia may indicate an obstruction in the device for whatever reason and needs to be explored. Polyneuropathy has been reported; evaluate for history/signs of and known risk factors before starting therapy. PRODUODOPA is high in sodium; considered especially in patients on a low salt diet. Caution is needed in concomitant administration of PRODUODOPA with the following medicinal products: Antihypertensives, antidepressants, COMT inhibitors, dopamine antagonists, MAO inhibitors, amantadine. Sympathomimetics may increase cardiovascular adverse events related to levodopa. Foscarbidopa is a potential inducer of CYP1A2 in vitro. Care should be taken when prescribing PRODUODOPA in combination with sensitive CYP1A2 substrates (e.g. caffeine). Review section of interactions with other medicinal products in SmPC for further details about these and a complete list of interactions. Fertility, pregnancy and lactation PRODUODOPA is not recommended during pregnancy. Breast-feeding should be discontinued during treatment with PRODUODOPA. Undesirable effects Summary of the safety profile The most frequent adverse reactions (≥10%) reported in all Phase 3 studies in patients exposed to PRODUODOPA were infusion site events (infusion site erythema, infusion site cellulitis, infusion site nodule, infusion site pain, infusion site oedema, infusion site reaction, and infusion site infection), hallucination, fall, and anxiety. This is not a complete summary of all safety information. Globally, prescribing information varies; please refer to your country specific product labeling for complete product prescribing and safety information. About AbbVie in Neuroscience At AbbVie, our commitment to preserving personhood of people around the world living with neurological and psychiatric disorders is unwavering. With more than three decades of experience in neuroscience, we are providing meaningful treatment options today and advancing innovation for the future. AbbVie's Neuroscience portfolio consists of approved treatments in neurological conditions, including migraine, movement disorders, and psychiatric disorders, along with a robust pipeline of transformative therapies. We have made a strong investment in research and are committed to building a deeper understanding of neurological and psychiatric disorders. Every challenge makes us more determined and drives us to discover and deliver advancements for those impacted by these conditions, their care partners, and clinicians. For more information, visit . About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @AbbVie on X (formerly Twitter), Facebook, Instagram, YouTube, and LinkedIn Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. References 1 PRODUODOPA® (foslevodopa/foscarbidopa solution for infusion) Summary of Product Characteristics. November 2023. 2 Soileau, M., et al. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. The Lancet Neurology. December 2022. 3 Armstrong, MJ. and Okun, MS. (2020). Diagnosis and Treatment of Parkinson Disease. A Review. JAMA 2020; 323(6): 548-560. 4 "What is Parkinson's?" Parkinson's Foundation. Available at: . Accessed: August 29, 2023. 5 Luquin M-R et al. Parkinson's Dis. 2018; 4047392. 6 Malaty IA et al. (2022). Does the 5-2-1 criteria identify patients with advanced Parkinson's disease? Real-world screening accuracy and burden of 5-2-1-positive patients in 7 countries. Gainsville: BCM Neurology. 7 "Wearing off and motor fluctuations". Parkinson's Europe. Available at . Accessed November 6, 2023. 8 Aldred, J., et al. Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinson's Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study. Journal of Neurology & Therapy. August 2023. 9 Rosebraugh, M., et al. Foslevodopa/foscarbidopa subcutaneous infusion maintains equivalent levodopa exposure to levodopa-carbidopa intestinal gel delivered to the jejunum. Science Direct. April 2022. SOURCE AbbVie

Clinical ResultPhase 3Drug ApprovalPhase 1Phase 2

26 May 2023

·www.drugs.com

The Most Common Depression Medications, Explained

FRIDAY, May 26, 2023 -- You've been diagnosed with depression. What's next? The cornerstone of treatment remains antidepressants, so it's likely your doctor will prescribe one for you, but which one might be best? You will join millions around the world who struggle with how to treat the mental health disorder. An estimated 3.8% of the global population experiences depression, according to the World Health Organization . The numbers are staggering, but when depression is left untreated, it can impair daily functioning, raise the risk of suicide and lower quality of life. Fortunately, there are many different types of antidepressants available, each with unique mechanisms of action, benefits and potential side effects. Here, experts will explore the most commonly prescribed depression medications, how they work and their common side effects. Depression medications Dr. Abid Nazeer, founder, chief medical officer and medical director of Advanced Psych Solutions in Naperville, Ill., stated, “If you don’t treat depression, there’s a risk that you may get through the day, but it will feel like a struggle. If it’s been adequately treated, you can have a much better day.” Meanwhile, Pardis Khosravi , a psychologist and clinical director at Children’s Health Council in California, said, “Depression is not something you can 'power through' or think your way out of with positive thoughts. It is a medical illness that left untreated can have a profound impact on your health, quality of life and daily functioning. Untreated depression increases the likelihood of risky behaviors such as substance use, self-harm and suicidal ideation and/or behaviors.” Although alternative therapies can be successful in treating depression, medication might become necessary in certain situations when other treatments have failed, depression symptoms interfere considerably with daily life, there is a history of mental health issues, or when a person feels too exhausted to pursue non-medication treatments. Here are some of the most common depression medications: Selective serotonin reuptake inhibitors (SSRIs) SSRIs are a class of medications used to treat depression by elevating serotonin levels in the brain, a crucial neurotransmitter that facilitates communication between nerve cells. The Mayo Clinic indicates that SSRIs prevent serotonin reabsorption into neurons, ensuring that more of the chemical messenger remains available to enhance signaling between brain cells. Additionally, SSRIs are known as selective agents because they primarily impact serotonin rather than other neurotransmitters. These SSRIs have received approval from the U.S. Food and Drug Administration for the treatment of depression: Citalopram (Celexa) Escitalopram (Lexapro) Fluoxetine (Prozac) Paroxetine (Paxil, Pexeva) Sertraline (Zoloft) While SSRIs effectively treat depression, they may also cause various side effects. Per an article published in the Primary Care Companion to the Journal of Clinic Psychology , SSRIs' most common side effects include gastrointestinal problems, sexual dysfunction, weight gain and sleep disturbances. Gastrointestinal side effects include nausea, diarrhea and abdominal pain, while sexual dysfunction includes decreased libido, erectile dysfunction and difficulty achieving orgasm. In rare cases, SSRIs may increase the risk of suicidal ideation, particularly in young people, some research has shown. Antidepressant medications SSRIs are not the only medications for depression: Tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) work by affecting other neurotransmitters. SSRIs generally have fewer side effects than these older antidepressants and are typically the first-line treatment for depression. However, the choice of medication depends on individual needs, and health care providers may recommend different types of antidepressants based on the patient's specific symptoms and medical history. Monoamine oxidase inhibitors (MAOIs) MAOIs are another type of antidepressant medication that blocks the enzyme monoamine oxidase, which breaks down neurotransmitters such as serotonin, norepinephrine and dopamine. By increasing the levels of these neurotransmitters, MAOIs can alleviate symptoms of depression. Some of the most common MAOIs include: Phenelzine (Nardil) Tranylcypromine (Parnate) Isocarboxazid (Marplan) Selegiline (Emsam) — available as a transdermal patch These medications can be effective in treating depression. However, the Mayo Clinic states that they are generally not considered first-line therapy due to their potential for serious side effects and interactions with certain foods and medications. Atypical antidepressants According to Mental Health America , atypical antidepressants are a diverse class of medications used to treat depression that do not fit neatly into other categories of antidepressants. They work by targeting multiple neurotransmitters in the brain, including serotonin, norepinephrine and dopamine, to improve mood and ease symptoms of depression. Some of the most commonly used atypical antidepressants include: Bupropion (Wellbutrin) Mirtazapine (Remeron) Trazodone (Desyrel) Vilazodone (Viibryd) Vortioxetine (Trintellix) Bupropion is known for its unique mechanism of action, which involves increasing the levels of norepinephrine and dopamine in the brain. Mirtazapine works by increasing the release of both serotonin and norepinephrine, while trazodone primarily affects serotonin levels. Vilazodone and vortioxetine are newer medications that target multiple neurotransmitters and effectively treat depression. These medications may be useful for individuals who have not responded to other types of antidepressants or who experience side effects from other medications. SOURCES: Abid Nazeer, MD, founder, chief medical officer and medical director, Advanced Psych Solutions, Naperville, Ill.; Pardis Khosravi, psychologist and clinical director, Children’s Health Council, Palo Alto, Calif. Posted May 2023

Drug Approval

100 Deals associated with Selegiline

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KEGG	Wiki	ATC	Drug Bank
D03731	Selegiline	N04BD01	DB01037

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Depressive Disorder, Major	US	Somerset Pharmaceuticals, Inc.	27 Feb 2006

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Cocaine-Related Disorders	Discovery	US	Somerset Pharmaceuticals, Inc.	01 Mar 2001

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00439413 (CTgov)	Phase 2	Nicotine Dependence	246	Placebo	lrybdaouoo(echsgapiup) = vwkteptbhk rgqblxtnwx (yfayobbnzz, hnaxhzmuwa - kwtlhpulhq)	-	13 Oct 2016
NCT01330030 (CTgov)	Phase 2	Nicotine Dependence	243	Selegiline (Drug Selegiline)	wgdcuajscp(desyrsydfm) = kwtqphclys xqoskwdrnm (pnqszuynlk, hbghzluwns - ugybqckkrd) View more	-	04 Apr 2016
				matching placebo (Matching Placebo)	wgdcuajscp(desyrsydfm) = sezijcabvb xqoskwdrnm (pnqszuynlk, ygoqbgcvoo - amtwwnyrai) View more
AAN2015	Phase 3	Parkinson Disease	603	Rotigotine+Selegiline	eewumzdgdw(sjidkcjnjo) = rotigotine+selegiline: 42%, placebo+selegiline: 15% qwlmofhope (wdsjhyvtwq ) View more	-	06 Apr 2015
				Placebo+Selegiline
NCT00535262 (CTgov)	Phase 4	Bipolar Disorder	3	EmSam	rqfgkdwejm(fowljspmyt) = hcgrppkoku srpipdicmt (hmwmhytxlu, dsujmlknzn - amybmhngyj) View more	-	28 Oct 2014
NCT00129311 (CTgov)	Phase 2	Smoking Cessation	101	Selegiline (Selegiline)	ftkijlathq(vhozwlnjdw) = oixgxowzmn bgnahfofgj (fuzjdmaiwn, beycsrfbvs - whmdanohtw) View more	-	16 Jul 2014
				placebo+Selegiline (Placebo)	ftkijlathq(vhozwlnjdw) = hhfgtenqgq bgnahfofgj (fuzjdmaiwn, exlgjnhddu - udyznxtwqd) View more
NCT00531947 (CTgov)	Phase 4	Depressive Disorder, Major	308	Placebo (Placebo)	gspkqkrgnn(fhygpwbmfa) = vfvfkmxkfz bycjcognsj (sdnclpfrzv, tpptdnumlm - rqboikmzah) View more	-	26 Jun 2013
				Selegiline Transdermal System (EMSAM)	gspkqkrgnn(fhygpwbmfa) = gpwbcybqfv bycjcognsj (sdnclpfrzv, pnejdmnfef - bqgaykhxwi) View more
P06.087 (AAN2012)	Not Applicable	Parkinson Disease	-	Rasagiline	jwvmesnsbk(zgmgmkdopo) = wrfizbsiiv pzupcosmvz (qnrwwtbpho )	Positive	23 Apr 2012
				Selegiline	jwvmesnsbk(zgmgmkdopo) = peasiwlaea pzupcosmvz (qnrwwtbpho )

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