New information of dopaminergic agents based on quantum chemistry calculations

Goode-Romero, Guillermo; Winnberg, Ulrika; Domı́nguez, Laura; Ibarra, Ilich A.; Vargas, Rubicelia; Winnberg, Elisabeth; Martı́nez, Ana

doi:10.1038/s41598-020-78446-4

Cited by 24 publications

(10 citation statements)

References 53 publications

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“…Results from Figure 2 indicate that most of the molecules are electron donors rather than electron acceptors. As mentioned previously [ 40 , 41 , 42 , 43 ], electron donor and electron acceptor capacity are both important factors in the prevention of oxidative stress. Free radicals are very reactive molecules that present an unpaired electron and produce oxidative stress.…”

Section: Resultsmentioning

confidence: 94%

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Electron Donor–Acceptor Capacity of Selected Pharmaceuticals against COVID-19

Martı́nez

2021

Antioxidants

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More than a year ago, the first case of infection by a new coronavirus was identified, which subsequently produced a pandemic causing human deaths throughout the world. Much research has been published on this virus, and discoveries indicate that oxidative stress contributes to the possibility of getting sick from the new SARS-CoV-2. It follows that free radical scavengers may be useful for the treatment of coronavirus 19 disease (COVID-19). This report investigates the antioxidant properties of nine antivirals, two anticancer molecules, one antibiotic, one antioxidant found in orange juice (Hesperidin), one anthelmintic and one antiparasitic (Ivermectin). A molecule that is apt for scavenging free radicals can be either an electron donor or electron acceptor. The results I present here show Valrubicin as the best electron acceptor (an anticancer drug with three F atoms in its structure) and elbasvir as the best electron donor (antiviral for chronic hepatitis C). Most antiviral drugs are good electron donors, meaning that they are molecules capable of reduzing other molecules. Ivermectin and Molnupiravir are two powerful COVID-19 drugs that are not good electron acceptors, and the fact that they are not as effective oxidants as other molecules may be an advantage. Electron acceptor molecules oxidize other molecules and affect the conditions necessary for viral infection, such as the replication and spread of the virus, but they may also oxidize molecules that are essential for life. This means that the weapons used to defend us from COVID-19 may also harm us. This study posits the idea that oxide reduction balance may help explain the toxicity or efficacy of these drugs. These results represent a further advance on the road towards understanding the action mechanisms of drugs used as possible treatments for COVID-19. Looking ahead, clinical studies are needed to define the importance of antioxidants in treating COVID-19.

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Section: Resultsmentioning

confidence: 94%

“…This definition is based on a simple charge transfer model expressed in terms of chemical potential and hardness. These chemical descriptors have been used successfully in many different chemical systems [ 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ].…”

Section: Computational Detailsmentioning

confidence: 99%

Electron Donor–Acceptor Capacity of Selected Pharmaceuticals against COVID-19

Martı́nez

2021

Antioxidants

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“…In a previous investigation, the DAM of agonists and antagonists of dopamine was reported. 14 Agonists and dopamine were located at the good electrondonor zone, while antagonists were found at the good electronacceptor zone. Agonists of dopamine possess similar electrontransfer properties than dopamine, but antagonists are the contrary.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

“…In spite of all these reports, there are no quantum chemical investigations concerning the properties of acetylcholine agonists, partial agonists, or antagonists focused to make a proper classification of these muscarinic drugs. It was previously reported 14 that an extensive study of many drugs has been proposed to treat schizophrenia and other neuropsychiatric disorders. The electron donor−acceptor properties were used to make a classification that can help in the design of new drugs.…”

Section: ■ Introductionmentioning

confidence: 99%

Electron Donor–Acceptor Properties of Different Muscarinic Ligands: On the Road to Control Schizophrenia

Goode-Romero

Domı́nguez

Martı́nez

2021

J. Chem. Inf. Model.

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Schizophrenia is a severe neuropsychiatric disorder that deteriorates perception, affection, and cognitive mental functions. The current treatments are mainly focused on the dopamine system, but the so-named dopamine hypothesis of schizophrenia fails to explain all the symptoms. Previous studies have shown that there is a reciprocal relationship between muscarinic acetylcholine receptors and dopamine receptor function. Some muscarinic ligands show antidopaminergic activity, and therefore, they should have some antipsychotic efficacy. In this work, conceptual density functional theory is employed to analyze the properties of acetylcholine’s agonists, partial agonists, or antagonists. The aim is to establish a classification of the antipsychotic-like or pro-psychotic activities of these molecules based on the electron-donor and electron-acceptor properties. Most of the agonists and antagonists are better electron donors and worse electron acceptors than partial agonists. We found that acetylcholine antagonists that clinically promote psychotic symptoms are good electron-donor molecules, and acetylcholine agonists that clinically relieve symptoms of psychosis are good electron donors. These results represent a further advance on the road to understanding the charge-transfer properties of drugs used as possible treatments for schizophrenia.

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“…Dopamine is a neurotransmitter that has an important role in human brain functions. Its dysregulation has been found to cause psychosis and mood disorders, as well as movement disorders, such as Parkinson’s disease and Huntington’s disease ( Goode-Romero et al, 2020 ). A variety of commonly prescribed antipsychotic drugs, such as aripiprazole, cariprazine and brexpiprazole, are partial agonists of dopamine receptors.…”

Section: Pharmacogenomic Studies Focusing On the Association Between Tardive Dyskinesia And Genes Involved In The Pharmacodynamicsmentioning

confidence: 99%

Genetic Factors Associated With Tardive Dyskinesia: From Pre-clinical Models to Clinical Studies

2022

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Tardive dyskinesia is a severe motor adverse event of antipsychotic medication, characterized by involuntary athetoid movements of the trunk, limbs, and/or orofacial areas. It affects two to ten patients under long-term administration of antipsychotics that do not subside for years even after the drug is stopped. Dopamine, serotonin, cannabinoid receptors, oxidative stress, plasticity factors, signaling cascades, as well as CYP isoenzymes and transporters have been associated with tardive dyskinesia (TD) occurrence in terms of genetic variability and metabolic capacity. Besides the factors related to the drug and the dose and patients’ clinical characteristics, a very crucial variable of TD development is individual susceptibility and genetic predisposition. This review summarizes the studies in experimental animal models and clinical studies focusing on the impact of genetic variations on TD occurrence. We identified eight genes emerging from preclinical findings that also reached statistical significance in at least one clinical study. The results of clinical studies are often conflicting and non-conclusive enough to support implementation in clinical practice.

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New information of dopaminergic agents based on quantum chemistry calculations

Cited by 24 publications

References 53 publications

Electron Donor–Acceptor Capacity of Selected Pharmaceuticals against COVID-19

Electron Donor–Acceptor Capacity of Selected Pharmaceuticals against COVID-19

Electron Donor–Acceptor Properties of Different Muscarinic Ligands: On the Road to Control Schizophrenia

Genetic Factors Associated With Tardive Dyskinesia: From Pre-clinical Models to Clinical Studies

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