The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.

01 Feb 2023·Graefe's Archive for Clinical and Experimental Ophthalmology

Studies on the interactions of retinal dopamine with choroidal thickness in the chicken

Article

Author: Mathis, Ute ; Schaeffel, Frank ; Liu, Hong ; Feldkaemper, Marita

AbstractPurposeRecently, an increasing number of studies relied on the assumption that visually induced changes in choroidal thickness can serve as a proxy to predict future axial eye growth. The retinal signals controlling choroidal thickness are, however, not well defined. We have studied the potential roles of dopamine, released from the retina, in the choroidal response in the chicken.MethodsChanges in retinal dopamine release and choroidal thickness changes were induced by intravitreal injections of either atropine (250 µg or 360 nMol), atropine combined with a dopamine antagonist, spiperone (500 µMol), or spiperone alone and were tracked by optical coherence tomography (OCT). To visually stimulate dopamine release, other chicks were exposed to flicker light of 1, 10, or 400 Hz (duty cycle 0.2) and choroidal thickness was tracked. In all experiments, dopamine and 3,4-Dihydroxyphenylacetic acid (DOPAC) were measured in vitreous, retina, and choroid by high-performance liquid chromatography with electrochemical detection (HLPC-ED). The distribution of the rate-limiting enzyme of dopamine synthesis, tyrosine hydroxylase (TH), neuronal nitric oxide synthase (nNOS), vascular endothelial growth factor (VEGF), and alpha2A adrenoreceptors (alpha2A-ADR) was studied in the choroid by immunofluorescence.ResultsThe choroid thickened strongly in atropine-injected eyes, less so in atropine + spiperone–injected eyes and became thinner over the day in spiperone alone-, vehicle-, or non-injected eyes. Flickering light at 20 lx, both 1 and 10 Hz, prevented diurnal choroidal thinning, compared to 400 Hz, and stimulated retinal dopamine release. Correlation analysis showed that the higher retinal dopamine levels or release, the thicker became the choroid. TH-, nNOS-, VEGF-, and alpha2A adrenoreceptor–positive nerve fibers were localized in the choroid around lacunae and in the walls of blood vessels with colocalization of TH and nNOS, and TH and VEGF.ConclusionsRetinal DOPAC and dopamine levels were positively correlated with choroidal thickness. TH-positive nerve fibers in the choroid were closely associated with peptides known to play a role in myopia development. Findings are in line with the hypothesis that dopamine is related to retinal signals controlling choroidal thickness.

01 Jun 2022·Saudi Journal of Biological SciencesQ3 · BIOLOGY

An in silico approach unveils the potential of antiviral compounds in preclinical and clinical trials as SARS-CoV-2 omicron inhibitors

Q3 · BIOLOGY

ArticleOA

Author: Lee, Joongku ; Bahadur Gurung, Arun ; Ajmal Ali, Mohammad ; Amina, Musarat ; Elshikh, Mohamed S ; Aref, Ibrahim

The increased transmissibility and highly infectious nature of the new variant of concern (VOC) that is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and lack of effective therapy need the rapid discovery of therapeutic antivirals against it. The present investigation aimed to identify antiviral compounds that would be effective against SARS-CoV-2 Omicron. In this study, molecular docking experiments were carried out using the recently reported experimental structure of omicron spike protein in complex with human angiotensin-converting enzyme 2 (ACE2) and various antivirals in preclinical and clinical trial studies. Out of 36 tested compounds, Abemaciclib, Dasatinib and Spiperone are the three top-ranked molecules which scored binding energies of -10.08 kcal/mol, -10.06 kcal/mol and -9.54 kcal/mol respectively. Phe338, Asp339, and Asp364 are crucial omicron receptor residues involved in hydrogen bond interactions, while other residues were mostly involved in hydrophobic interactions with the lead molecules. The identified lead compounds also scored well in terms of drug-likeness. Molecular dynamics (MD) simulation, essential dynamics (ED) and entropic analysis indicate the ability of these molecules to modulate the activity of omicron spike protein. Therefore, Abemaciclib, Dasatinib and Spiperone are likely to be viable drug-candidate molecules that can block the interaction between the omicron spike protein and the host cellular receptor ACE2. Though our findings are compelling, more research into these molecules is needed before they can be employed as drugs to treat SARS-CoV-2 omicron infections.

100 Deals associated with Spiperone

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KEGG	Wiki	ATC	Drug Bank
D01051	Spiperone	N05A	-

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Indication	Country/Location	Organization	Date
Schizophrenia	JP	Sannova KK	05 Sep 1968
Schizophrenia	JP	Janssen Global Services LLC	05 Sep 1968
Schizophrenia	JP	Alfresa Pharma Corp.	05 Sep 1968

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ARVO2010	Not Applicable	Myopia	-	Spiperone	vmyfadvcxz(akplfwtlge) = pneryxiaro ggyrcwgfbu (irffrcrobd, 0.8)	Negative	01 Apr 2010
				MT3 + Spiperone	vmyfadvcxz(akplfwtlge) = eqjzlcseya ggyrcwgfbu (irffrcrobd, 1.2)

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