scholarly journals Involvement of Cholinergic and Opioid System inγ-Terpinene-Mediated Antinociception

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Flávia Franceli de Brito Passos ◽  
Everton Moraes Lopes ◽  
Jonas Moura de Araújo ◽  
Damião Pergentino de Sousa ◽  
Leiz Maria C. Veras ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Structural Similarity ◽  
Mechanisms Of Action ◽  
Sedative Effect ◽  
New Drugs ◽  
Pharmacological Properties ◽  
Depressant Effect ◽  
Muscle Relaxant Activity ◽  
Opioid Systems ◽  
Central Depressant

The literature shows that the monoterpenes are great candidates for the development of new drugs for the treatment of various pathological processes, including painful conditions. The gamma terpinene (γ-TPN) is a monoterpene present in plant species that have multiple pharmacological properties and has structural similarity to antinociceptive monoterpenes, such as limonene and alpha-phellandrene. Theγ-TPN molecular mass was evaluated by mass spectrometry and showed a pseudomolecular ion withm/z137.0 Da. The animals did not present any signs of acute toxicity at 2 g/kg, p.o.γ-TPN (1.562 to 50 mg/kg, p.o.) showed an antinociceptive effect in the formalin, capsaicin, and glutamate tests.γ-TPN has antinociceptive action when administered by others routes in glutamate test. To eliminate a possible sedative effect ofγ-TPN, the open field and rota-rod test were conducted and theγ-TPN did not show muscle relaxant activity or central depressant effect. To investigate the mechanisms of action, the animals were pretreated with naloxone, glibenclamide, atropine, mecamylamine, or L-arginine in the glutamate test.γ-TPN antinociception was inhibited in the presence of naloxone, glibenclamide, atropine, and mecamylamine. The results suggest that theγ-TPN (p.o.) produced antinociceptive effect in models of chemical nociception through the cholinergic and opioid systems involvement.

scholarly journals GenusCaulophyllum: An Overview of Chemistry and Bioactivity

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Yong-Gang Xia ◽  
Guo-Yu Li ◽  
Jun Liang ◽  
Bing-You Yang ◽  
Shao-Wa Lü ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Membrane ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Pharmacological Properties ◽  
Cell Membrane Chromatography ◽  
Action Mechanisms ◽  
Naturally Occurring ◽  
Activity Screening ◽  
Point Of Reference

Recently, some promising advances have been achieved in understanding the chemistry, pharmacology, and action mechanisms of constituents from genusCaulophyllum. Despite this, there is to date no systematic review of those of genusCaulophyllum. This review covers naturally occurring alkaloids and saponins and those resulting from synthetic novel taspine derivatives. The paper further discussed several aspects of this genus, including pharmacological properties, mechanisms of action, pharmacokinetics, and cell membrane chromatography for activity screening. The aim of this paper is to provide a point of reference for pharmaceutical researchers to develop new drugs from constituents ofCaulophyllumplants.

GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors

2018 ◽  
Vol 24 (17) ◽  
pp. 1839-1844 ◽  
Author(s):  
Ahmad Tarmizi Che Has ◽  
Mary Chebib
Keyword(s):  
Central Nervous System ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
New Drugs ◽  
Pharmacological Properties ◽  
Receptor Complex ◽  
The Third ◽  
Γ Subunit ◽  
Subunit Stoichiometry ◽  
The Central Nervous System

GABAA receptors are members of the Cys-loop family of ligand-gated ion channels which mediate most inhibitory neurotransmission in the central nervous system. These receptors are pentameric assemblies of individual subunits, including α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3. The majority of receptors are comprised of α, β and γ or δ subunits. Depending on the subunit composition, the receptors are located in either the synapses or extrasynaptic regions. The most abundant receptors are α1βγ2 receptors, which are activated and modulated by a variety of pharmacologically and clinically unrelated agents such as benzodiazepines, barbiturates, anaesthetics and neurosteroids, all of which bind at distinct binding sites located within the receptor complex. However, compared to αβγ, the binary αβ receptors lack a benzodiazepine α-γ2 interface. In pentameric αβ receptors, the third subunit is replaced with either an α1 or a β3 subunit leading to two distinct receptors that differ in subunit stoichiometry, 2α:3β or 3α:2β. The consequence of this is that 3α:2β receptors contain an α-α interface whereas 2α:3β receptors contain a β-β interface. Apart from the replacement of γ by α1 or β3 in binary receptors, the incorporation of ε subunit into GABAA receptors might be more complicated. As the ε subunit is not only capable of substituting the γ subunit, but also replacing the α/β subunits, receptors with altered stoichiometry and different pharmacological properties are produced. The different subunit arrangement of the receptors potentially constructs novel binding sites which may become new targets of the current or new drugs.

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations

2020 ◽  
Vol 20 (14) ◽  
pp. 1264-1273 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Walter Verrusio ◽  
Mauro Cacciafesta ◽  
Maria Luisa Mangoni
Keyword(s):  
Antimicrobial Peptides ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Lead Compounds ◽  
Bacterial Pathogenicity ◽  
Growth Inhibitory ◽  
Resistant Strains ◽  
Conventional Antibiotics

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

scholarly journals Risks and risk management in modern multiple sclerosis immunotherapeutic treatment

2019 ◽  
Vol 12 ◽  
pp. 175628641983657 ◽  
Author(s):  
Luisa Klotz ◽  
Joachim Havla ◽  
Nicholas Schwab ◽  
Reinhard Hohlfeld ◽  
Michael Barnett ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Side Effect ◽  
Paradigm Shift ◽  
Mechanisms Of Action ◽  
Optimal Choice ◽  
New Drugs ◽  
Comprehensive Overview ◽  
Disease Modifying Drugs ◽  
Practical Recommendations ◽  
Target Effects

In recent years, there has been a paradigm shift in the treatment of multiple sclerosis (MS) owing to the approval of a number of new drugs with very distinct mechanisms of action. All approved disease-modifying drugs primarily work directly on the immune system. However, the identification of an ‘optimal choice’ for individual patients with regard to treatment efficacy, treatment adherence and side-effect profile has become increasingly complex including conceptual as well as practical considerations. Similarly, there are peculiarities and specific requirements with regard to treatment monitoring, especially in relation to immunosuppression, the development of secondary immune-related complications, as well as the existence of drug-specific on- and off-target effects. Both classical immunosuppression and selective immune interventions generate a spectrum of potential therapy-related complications. This article provides a comprehensive overview of available immunotherapeutics for MS and their risks, detailing individual mechanisms of action and side-effect profiles. Furthermore, practical recommendations for patients treated with modern MS immunotherapeutics are provided.

New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings

2008 ◽  
Vol 9 (12) ◽  
pp. 1157-1165 ◽  
Author(s):  
Enrique M Ocio ◽  
María-Victoria Mateos ◽  
Patricia Maiso ◽  
Atanasio Pandiella ◽  
Jesús F San-Miguel
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Mechanisms Of Action ◽  
Clinical Findings ◽  
New Drugs

scholarly journals Betanin: a promising molecule for biomedical applications

2020 ◽  
Vol 10 (3) ◽  
pp. 5392-5399
Keyword(s):  
Positive Impact ◽  
Pharmaceutical Products ◽  
Free Radical Scavenger ◽  
Biologically Active ◽  
New Drugs ◽  
Radical Scavenger ◽  
Therapeutic Effects ◽  
Pharmacological Properties ◽  
Natural Colorant ◽  
Anti Oxidant

Plants with medicinal properties possess beneficial influences on health and disease. Different plant parts and extracts carry valuable active ingredients with pharmacological properties that lead to developing new drugs. Terminalia bellirica is among those plants that have been formulated as pharmaceutical products. This is attributed to its biologically active phenolics and tannins exhibiting analgesic, anti-hypertensive, anti-microbial, anti-diabetic, anti-oxidant, as well as, other pharmacological properties. Beetroot has been shown to be rich in nitrates with a positive impact on the cardiovascular system. Beetroot contains a number of useful ingredients as the free-radical scavenger ascorbic acid, the anti-inflammatory flavonoids and the anti-oxidant carotenoids. Moreover, beetroot is rich in the natural colorant betalains that are further classified into betacyanins and betaxanthins. Betanin, is one of the major constituents of beetroots that have been postulated to possess significant beneficial therapeutic effects in a number of conditions and diseases. However, several studies have demonstrated the relatively poor bioavailability of betanin upon oral administration. In the current review we aim to highlight some of the latest researches dealing with the therapeutic properties of betanin in different disease conditions, the possible mechanistic pathways beyond such beneficial effects and plausible strategies capable of enhancing its stability and bioavailability.

Peripheral interactions between cannabinoid and opioid systems contribute to the antinociceptive effect of crotalphine

Toxicon ◽  
2016 ◽  
Vol 116 ◽  
pp. 72-73
Author(s):  
Y. Cury ◽  
G. Picolo ◽  
F.C. Machado ◽  
A.S. Heimann ◽  
C. Remuzgo ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Opioid Systems

Anti-Malarial Drug Resistance

2022 ◽  
pp. 233-250
Author(s):  
Manish Kumar Dwivedi ◽  
Prashant Kumar Singh
Keyword(s):  
Natural Products ◽  
Protozoan Parasite ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Efficacy And Safety ◽  
Infected Female ◽  
Traditional Medicines ◽  
Anopheles Mosquitoes ◽  
Synthetic Drugs ◽  
Life Threatening

Malaria is a life-threatening infectious disease caused by a protozoan parasite of the genus Plasmodium. It is transmitted through the bites of infected female Anopheles mosquitoes. The global burden is estimated to be around 219 million cases in 87 countries. Natural compounds have been used primarily in the traditional medicine for thousands of years. For the treatment of malaria, natural products were used until the development of synthetic drugs, and most of the currently available anti-malarial drugs have been derived based on the compounds from these traditional medicinal plants. The current chapter tries to briefly indicate the emerging resistance against anti-malarial drugs and to discuss the recent research on natural products that have been evaluated for anti-malarial activity. Rigorous evaluation of the efficacy and safety of traditional medicines is required along with identification of active constituents in order to develop new drugs with novel mechanisms of action.

scholarly journals PROMISCUOUS 2.0: a resource for drug-repositioning

2020 ◽  
Vol 49 (D1) ◽  
pp. D1373-D1380
Author(s):  
Kathleen Gallo ◽  
Andrean Goede ◽  
Andreas Eckert ◽  
Barbara Moahamed ◽  
Robert Preissner ◽  
...  
Keyword(s):  
Side Effects ◽  
Small Molecules ◽  
User Experience ◽  
Drug Target ◽  
Drug Repositioning ◽  
Dynamic Network ◽  
Structural Similarity ◽  
New Drugs ◽  
Entry Level ◽  
Development Costs

Abstract The development of new drugs for diseases is a time-consuming, costly and risky process. In recent years, many drugs could be approved for other indications. This repurposing process allows to effectively reduce development costs, time and, ultimately, save patients’ lives. During the ongoing COVID-19 pandemic, drug repositioning has gained widespread attention as a fast opportunity to find potential treatments against the newly emerging disease. In order to expand this field to researchers with varying levels of experience, we made an effort to open it to all users (meaning novices as well as experts in cheminformatics) by significantly improving the entry-level user experience. The browsing functionality can be used as a global entry point to collect further information with regards to small molecules (∼1 million), side-effects (∼110 000) or drug-target interactions (∼3 million). The drug-repositioning tab for small molecules will also suggest possible drug-repositioning opportunities to the user by using structural similarity measurements for small molecules using two different approaches. Additionally, using information from the Promiscuous 2.0 Database, lists of candidate drugs for given indications were precomputed, including a section dedicated to potential treatments for COVID-19. All the information is interconnected by a dynamic network-based visualization to identify new indications for available compounds. Promiscuous 2.0 is unique in its functionality and is publicly available at http://bioinformatics.charite.de/promiscuous2.

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