scholarly journals CGRP Receptor Antagonists and 5-HT1F Receptor Agonist in the Treatment of Migraine

2021 ◽  
Vol 10 (7) ◽  
pp. 1429
Author(s):  
Matilde Capi ◽  
Valerio De Angelis ◽  
Donatella De Bernardini ◽  
Ottavia De Luca ◽  
Fabiola Cipolla ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Management ◽  
Receptor Agonist ◽  
Preventive Treatment ◽  
New Drugs ◽  
Cgrp Receptor ◽  
Therapeutic Approaches ◽  
New Class ◽  
Cgrp Receptor Antagonists

Discovering that calcitonin-related peptide (CGRP) plays a key role in the complex pathophysiology of migraine has allowed us to make great strides in the development of new approaches for acute and preventive treatment. This evidence has led to the development of small molecules antagonist molecules of the CGRP receptor (“gepants”) and of a new class of medications called “Ditans”. This review presents the data from clinical trials reporting the efficacy, safety, and tolerability of the new drugs used in the treatment of migraines. Evidences show that therapeutic approaches targeted to CGRP have the potential to transform the clinical management of migraine, even though its appropriate place has yet to be determined with accuracy.

Current management: migraine headache

CNS Spectrums ◽  
2017 ◽  
Vol 22 (S1) ◽  
pp. 1-13 ◽  
Author(s):  
Stephen D. Silberstein
Keyword(s):  
Migraine Headache ◽  
Acute Treatment ◽  
Receptor Agonist ◽  
Preventive Treatment ◽  
Pharmacologic Treatment ◽  
Migraine Prevention ◽  
Cgrp Receptor ◽  
Current Management ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists

Migraine varies in its frequency, severity, and impact; treatment should consider these variations and the patient’s needs and goals. Migraine pharmacologic treatment may be acute (abortive) or preventive (prophylactic), and patients often require both. New medication devices are available or in development, including an intracutaneous, microneedle system of zolmitriptan and sumatriptan, and breath-powered powder sumatriptan intranasal treatment. Lasmiditan, a 5-HT1F receptor agonist, is in development for acute treatment, as are small molecule calcitonin gene-related peptide (CGRP) receptor antagonists (Gepants) for acute and preventive treatment. Antibodies to CGRP and its receptor are being developed for migraine prevention. All 4 treatments are effective and have, as of yet, no safety concerns.

The Therapeutic Impact of New Migraine Discoveries

2019 ◽  
Vol 26 (34) ◽  
pp. 6261-6281 ◽  
Author(s):  
László Vécsei ◽  
Melinda Lukács ◽  
János Tajti ◽  
Ferenc Fülöp ◽  
József Toldi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Preventive Treatment ◽  
Therapeutic Strategies ◽  
Migraine Treatment ◽  
Preclinical Studies ◽  
Therapeutic Approaches ◽  
Trigeminovascular System ◽  
Glutamate Receptor Antagonists

Background: Migraine is one of the most disabling neurological conditions and associated with high socio-economic costs. Though certain aspects of the pathomechanism of migraine are still incompletely understood, the leading hypothesis implicates the role of the activation of the trigeminovascular system. Triptans are considered to be the current gold standard therapy for migraine attacks; however, their use in clinical practice is limited. Prophylactic treatment includes non-specific approaches for migraine prevention. All these support the need for future studies in order to develop innovative anti-migraine drugs. Objective: The present study is a review of the current literature regarding new therapeutic lines in migraine research. Methods: A systematic literature search in the database of PUBMED was conducted concerning therapeutic strategies in a migraine published until July 2017. Results: Ongoing clinical trials with 5-HT1F receptor agonists and glutamate receptor antagonists offer promising new aspects for acute migraine treatment. Monoclonal antibodies against CGRP and the CGRP receptor are revolutionary in preventive treatment; however, further long-term studies are needed to test their tolerability. Preclinical studies show positive results with PACAP- and kynurenic acid-related treatments. Other promising therapeutic strategies (such as those targeting TRPV1, substance P, NOS, or orexin) have failed to show efficacy in clinical trials. Conclusion: Due to their side-effects, current therapeutic approaches are not suitable for all migraine patients. Especially frequent episodic and chronic migraine represents a therapeutic challenge for researchers. Clinical and preclinical studies are needed to untangle the pathophysiology of migraine in order to develop new and migraine-specific therapies.

scholarly journals Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Haiying Lu ◽  
Qiaodan Zhou ◽  
Jun He ◽  
Zhongliang Jiang ◽  
Cheng Peng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Small Molecules ◽  
Protein Interactions ◽  
Clinical Studies ◽  
New Drugs ◽  
Protein Protein Interactions ◽  
The Past ◽  
Recent Advances ◽  
Novel Drugs

Abstract Protein–protein interactions (PPIs) have pivotal roles in life processes. The studies showed that aberrant PPIs are associated with various diseases, including cancer, infectious diseases, and neurodegenerative diseases. Therefore, targeting PPIs is a direction in treating diseases and an essential strategy for the development of new drugs. In the past few decades, the modulation of PPIs has been recognized as one of the most challenging drug discovery tasks. In recent years, some PPIs modulators have entered clinical studies, some of which been approved for marketing, indicating that the modulators targeting PPIs have broad prospects. Here, we summarize the recent advances in PPIs modulators, including small molecules, peptides, and antibodies, hoping to provide some guidance to the design of novel drugs targeting PPIs in the future.

Novel Therapeutic Approaches and Treatment Targets for Psoriatic Arthritis

2020 ◽  
Vol 22 (1) ◽  
pp. 85-98
Author(s):  
Devis Benfaremo ◽  
Valentino Paci ◽  
Michele Maria Luchetti ◽  
Armando Gabrielli
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Joint Damage ◽  
Janus Kinase ◽  
New Drugs ◽  
The Novel ◽  
Therapeutic Approaches ◽  
Biological Drugs ◽  
Safety Issues ◽  
Extracutaneous Manifestation

Background: Psoriatic Arthritis (PsA) is the most common extracutaneous manifestation of psoriasis. This chronic inflammatory arthritis is burdened with significant morbidity, leading to irreversible joint damage and disability. In recent years, a deeper understating of its pathogenesis has led to the development of several new drugs targeting different pathways. Objectives: This review aims to highlight the clinical efficacy and safety of the novel agents that have become recently available for the treatment of PsA, as well as new promising therapeutic targets that are being evaluated in clinical trials. Methods: For the purpose of this narrative review, we searched in the MEDLINE and ClinicalTrials. gov databases. Results: After the introduction of the first biological drugs targeting Tumor Necrosis Factor (TNF), several other drugs with different targets have been developed, including anti-Interleukin (IL) 12/23p40, anti-IL17, and, more recently, anti-IL23p19 agents. Conclusions: Data supporting the efficacy of different agents in the major domains of PsA, as well as their safety issues, are summarized here. Finally, the current pipeline, including several novel nonbiological small molecules, such as Janus kinase (JAK) inhibitors, that are currently being evaluated in clinical trials are also presented. Discussion: The availability of newer therapeutic agents has substantially changed the treatment strategy for PsA. In the future, a personalized treatment approach will probably achieve better control of disease manifestations.

scholarly journals Pulmonary Tuberculosis: Focus on the Fluoroquinolones

2010 ◽  
Vol 2 ◽  
pp. CMT.S1974
Author(s):  
Stefan Goldberg ◽  
Philip LoBue
Keyword(s):  
Clinical Trials ◽  
Bacterial Infections ◽  
Community Acquired Pneumonia ◽  
New Drugs ◽  
Treatment Regimens ◽  
New Class ◽  
Drug Intolerance ◽  
Tb Treatment ◽  
Fluoroquinolone Antibiotics ◽  
The 1960S

Fluoroquinolone antibiotics are relatively new drugs in anti-tuberculosis (TB) treatment, with the potential to become the first new class of drugs to be recommended for routine treatment since rifamycins in the 1960s. Later generation fluoroquinolones, including levofloxacin, gatifloxacin, and moxifloxacin have been found to be safe and well-tolerated in observational studies and phase 2 clinical trials, except for a risk of severe dysglycemias with gatifloxacin. These drugs currently are used as second-line agents in treatment of TB cases with drug resistance and drug intolerance, and empirically in treatment of infected contacts of patients with multi-drug resistant TB. Widespread use of fluoroquinolones for treatment of community acquired pneumonia and other bacterial infections is leading to the emergence and spread of strains of Mycobacterium tuberculosis that are fluoroquinolone-resistant, putting at risk the potential effectiveness of these drugs against TB. Clinical trials are under way to determine whether fluoroquinolone-based treatment regimens can shorten the duration of TB therapy. The ultimate contributions of fluoroquinolones to TB control remain to be determined.

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1(MCL1)

2019 ◽  
Author(s):  
James Papatzimas ◽  
Evgueni Gorobets ◽  
Ranjan Maity ◽  
Mir Ishruna Muniyat ◽  
Justin L. MacCallum ◽  
...  
Keyword(s):  
Small Molecules ◽  
E3 Ligase ◽  
Myeloid Cell ◽  
Cell Leukemia ◽  
New Class ◽  
Apoptotic Protein ◽  
Family Protein ◽  
Ubiquitination Pathway

<div> <div> <div> <p>Here we show the development of heterobifunctional small molecules capable of selectively targeting MCL1 using a Proteolysis Targeting Chimera (PROTAC) methodology leading to successful degradation. We have confirmed the involvement of the E3 ligase CUL4A-DDB1 cereblon (CRBN) ubiquitination pathway, making these PROTACs a first step toward a new class of anti-apoptotic BCL-2 family protein degraders. </p> </div> </div> </div>

Conjugates of Classical DNA/RNA Binder with Nucleobase: Chemical, Biochemical and Biomedical Applications

2019 ◽  
Vol 26 (30) ◽  
pp. 5609-5624
Author(s):  
Dijana Saftić ◽  
Željka Ban ◽  
Josipa Matić ◽  
Lidija-Marija Tumirv ◽  
Ivo Piantanida
Keyword(s):  
Molecular Weight ◽  
Small Molecules ◽  
Biomedical Applications ◽  
Protein Targets ◽  
New Class ◽  
Rna Targets ◽  
Covalently Linked ◽  
Structural Aspects

: Among the most intensively studied classes of small molecules (molecular weight < 650) in biomedical research are small molecules that non-covalently bind to DNA/RNA, and another intensively studied class is nucleobase derivatives. Both classes have been intensively elaborated in many books and reviews. However, conjugates consisting of DNA/RNA binder covalently linked to nucleobase are much less studied and have not been reviewed in the last two decades. Therefore, this review summarized reports on the design of classical DNA/RNA binder – nucleobase conjugates, as well as data about their interactions with various DNA or RNA targets, and even in some cases protein targets are involved. According to these data, the most important structural aspects of selective or even specific recognition between small molecule and target are proposed, and where possible related biochemical and biomedical aspects were discussed. The general conclusion is that this, rather new class of molecules showed an amazing set of recognition tools for numerous DNA or RNA targets in the last two decades, as well as few intriguing in vitro and in vivo selectivities. Several lead research lines show promising advancements toward either novel, highly selective markers or bioactive, potentially druggable molecules.

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