G-Proteins Agonists and NO/cGMP Blockers: Unexplored Frontiers in the Pharmaceutical Industry

Évora, Paulo Roberto Barbosa

doi:10.5935/abc.20170139

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…Myocardial ischemia and reperfusion selectively impair receptor-mediated NO release. However, the ability of the endothelial cell to produce NO or generate endothelium-dependent relaxation to non-nitric oxide-dependent agonists remains intact [47,48].…”

Section: Pathophysiology Of Irimentioning

confidence: 99%

“…Even considering its safety at low doses, but the medical literature insists that it has not been submitted to any trial. However, it is mandatory to emphasize its new use and not its use as rescue therapy [47].…”

Section: Therapeutics: the Pharmacological Approachmentioning

confidence: 99%

“…Better microvascular integrity was observed in the presence of MB, as opposed to severe damage to animals that were infused with only NE [302]. Therefore, MB would be an option for the prevention of direct organ damage by adrenergic agents, although it still remains an unexplored frontier by the pharmaceutical industry [47]. Levy and colleagues wrote an excellent review article about the “past, present and future” of vasoplegia treatment and expressed some concerns about the use of MB [303].…”

Section: Therapeutics: the Pharmacological Approachmentioning

confidence: 99%

See 2 more Smart Citations

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

Soares

Losada

Jordani

et al. 2019

IJMS

223

180

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Ischemia/reperfusion injury (IRI) permeates a variety of diseases and is a ubiquitous concern in every transplantation proceeding, from whole organs to modest grafts. Given its significance, efforts to evade the damaging effects of both ischemia and reperfusion are abundant in the literature and they consist of several strategies, such as applying pre-ischemic conditioning protocols, improving protection from preservation solutions, thus providing extended cold ischemia time and so on. In this review, we describe many of the latest pharmacological approaches that have been proven effective against IRI, while also revisiting well-established concepts and presenting recent pathophysiological findings in this ever-expanding field. A plethora of promising protocols has emerged in the last few years. They have been showing exciting results regarding protection against IRI by employing drugs that engage several strategies, such as modulating cell-surviving pathways, evading oxidative damage, physically protecting cell membrane integrity, and enhancing cell energetics.

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Section: Pathophysiology Of Irimentioning

confidence: 99%

Section: Therapeutics: the Pharmacological Approachmentioning

confidence: 99%

Section: Therapeutics: the Pharmacological Approachmentioning

confidence: 99%

See 1 more Smart Citation

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

Soares

Losada

Jordani

et al. 2019

IJMS

223

180

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show abstract

“…As mentioned above, when guanylate cyclase is blocked, NO levels remain elevated but are inactive. Furthermore, guanylate cyclase, when inactivated, prevents the conversion of GTP into cGMP, which, in addition to reducing vasodilation, also facilitates the action of noradrenaline via cAMP since the cGMP pathway, when little activated, releases cAMP [44]. Furthermore, in the MB group, vasopressors showed a strong and direct correlation with IL-10, which also affects nitrate reduction [45,46].…”

Section: Discussionmentioning

confidence: 99%

Methylene blue therapy versus standard treatment for acute-phase septic shock: a pilot randomized controlled trial

Luis-Silva,

Menegueti,

Peres

et al. 2024

Preprint

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Purpose Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase (NOS). Objective To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to that in the control group. Methods This was a 1:1 randomized clinical trial of two groups (methylene blue and control). We used MB after fluid replacement, vasopressors and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 hours. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 minutes (T2), 2 hours (T3), 24 hours (T4), 48 hours after the infusion started (T5) and 24 hours after weaning (T6). Results Methylene blue therapy started within 72 hours of septic shock. The methylene blue group showed an immediate reduction in NOR dosage, earlier reduction in VAS dosage, and higher IL-10 levels compared to the control group. Integrative network analysis highlighted NO and IL-10's roles in coordinating correlations with "Hemodynamic Monitoring" in the control and methylene blue groups, respectively. Conclusion Early methylene blue (MB) administration alongside standard septic shock treatment reduces vasopressor doses, possibly involving nitric oxide (NO) mechanisms. A possible mechanism of action may involve modulation of inflammatory and anti-inflammatory mediators, enhancing immune response. However, larger and longer studies are needed for validation. Trial registration: Clinical registration: https://ensaiosclinicos.gov.br/rg/RBR-96584w4.

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“…MB is the oldest drug infused in humans, is cheap, and is not patented for industrial use, but the medical literature insists that it has not been the subject of any sizeable clinical trials, even considering its safety at low doses. However, it is mandatory to use it early, not as rescue therapy [ 3 ].…”

mentioning

confidence: 99%

Blocking soluble guanylate cyclase could be the present and future of NO/cGMP inhibition for vasoplegia treatment

Évora

2018

Crit Care

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G-Proteins Agonists and NO/cGMP Blockers: Unexplored Frontiers in the Pharmaceutical Industry

Cited by 4 publications

References 8 publications

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

Methylene blue therapy versus standard treatment for acute-phase septic shock: a pilot randomized controlled trial

Blocking soluble guanylate cyclase could be the present and future of NO/cGMP inhibition for vasoplegia treatment

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