É aquilo que digo ha dias decadas, as drogas destroem o que as pessoas têm de bom.
As a pharmacologist, I would like to express some concerns about the possible use of reserpine in this context. Reserpine is an old, well known anti-hypertensive drug, with a peculiar ability to counteract the sympathetic nervous system at both central and peripheral levels. Mechanistically, it inhibits the vesicular monoamine transporter 2 (VMAT2), preventing the accumulation of catecholamines and serotonin into the synaptic vesicles of the adrenergic neurons. Its use has been largely supplanted by other treatments that have shown equal or superior efficacy together with greater tolerability (6,7). Reserpine shows a peculiar, dose-dependent toxicity profile, characterized by sedation, nasal stuffiness, severe depression, even long-lasting after stopping treatment, gastrointestinal disorders, hyperprolactinemia, bradycardia and other cardiac arrhythmias, parkinsonism (
. The putative antiviral activity of reserpine has not been tested in vivo and no indication about effective doses exists. By impairing the sympathetic control, a dose range similar to that used in antihypertensive therapy may be harmful in critically ill patients with COVID-19. Multiple drug interactions may also occur, such as with adrenaline or other sympathomimetic amines, antiarrhythmic drugs, and sedative drugs like dexmedetomidine, clonidine, which are increasingly used in intensive care units.
For these reasons, we have not included reserpine and other drugs with similar potential in our review. However, we agree that further research is needed to deepen the knowledge of the SARS-CoV-2 exocytosis pathways and may represent a chance of finding new weapons against this global threat.
Conflict of interest:
Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article
Article information
Acta Biomed. 2020; 91(3): e2020049.
Published online 2020 Sep 7. doi: 10.23750/abm.v91i3.10108
PMCID: PMC7716991
PMID: 32921741
Francesco Potìcorresponding author
Dipartimento di Medicina e Chirurgia – Unità di Neuroscienze dell’Università di Parma
Inversamente, as estatinas podem ter algum efeito benefico a nivel mental, com mais dopamina.
Mais dopamina, mais drive.
Mas ha casos tambem que as estatinas podem por algumas pessoas mais neuroticas. Talvez por excesso de dopamina.
Mas nunca tinha lido nada sobre este VMAT2
The identification of an effective disease-modifying treatment for the neurodegenerative progression in Parkinson's disease (PD) remains a major challenge. Epidemiological studies have reported that intake of statins, cholesterol lowering drugs, could be associated to a reduced risk of developing PD. In-vivo studies suggest that statins may reduce the severity of dopaminergic neurodegeneration. We have investigated the trophic potential of statins and their impact on the expression of dopaminergic synaptic markers and dopamine (DA) transport function in SH-SY5Y cells. Our findings show that statin treatment induces neurite outgrowth involving a specific effect on the complexity of the neurite branching pattern. Statins increased the levels of presynaptic dopaminergic biomarkers such as vesicular monoamine transporter 2 (VMAT2), synaptic vesicle glycoproteins 2A and 2C (SV2C) and synaptogyrin-3 (SYNGR3). Gene expression analysis confirmed a rapid statin-induced up-regulation of VMAT2-, SV2C- and SYNGR3-mRNA levels. Assessment of [(3) H]DA transport in statin-treated cells showed a reduction in DA uptake concomitant to a modification of VMAT2 pharmacological properties. We also observed a nuclear translocation of the sterol regulatory element-binding protein 1 (SREBP-1). Our results suggest that statins induce phenotypic changes in dopaminergic cells characterized by an increase of growth, complexity of structural synaptic elements and expression of key presynaptic proteins with functional impact on the DA transport capacity. Statin-induced changes are likely the result of a downstream modulation of SREBP-1 pathway. Overall, these mechanisms may contribute to the neuroprotective or neurorestorative effects observed in the dopaminergic system and strengthen the therapeutic potential of statins for PD. This article is protected by copyright. All rights reserved.
