Systolic blood pressure as a potential target of sigma‐1 receptor agonist therapy

Cohen, Jordana B.; Perlis, Michael L.; Townsend, Raymond R.

doi:10.1111/jch.13197

Cited by 7 publications

(2 citation statements)

References 10 publications

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“…Animal and human studies show that agonists of the sigma-1 receptor cause vasodilation and systolic BP fall due to nitric oxide release from endothelial and neuronal nitric oxide synthases. This suggests a potential application of sigma agonists in antihypertensive drug treatments ( 83 , 84 ). Such effects may be especially relevant for fluvoxamine, fluoxetine, and escitalopram, which are strong agonists of the sigma-1 receptor but not sertraline, which, despite a high affinity for the sigma-1 receptor, only acts as a mild antagonist, making its effect on BP overall low ( 83 ).…”

Section: Methodsmentioning

confidence: 94%

Antidepressant Drugs Effects on Blood Pressure

Calvi

Fischetti

Verzicco

et al. 2021

Front. Cardiovasc. Med.

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Individuals suffering from depressive disorders display a greater incidence of hypertension compared with the general population, despite reports of the association between depression and hypotension. This phenomenon may depend, at least in part, on the use of antidepressant drugs, which may influence blood pressure through different effects on adrenergic and serotoninergic pathways, as well as on histaminergic, dopaminergic, and cholinergic systems. This review summarizes extant literature on the effect of antidepressant drugs on blood pressure. Selective serotonin reuptake inhibitors are characterized by limited effects on autonomic system activity and a lower impact on blood pressure. Thus, they represent the safest class—particularly among elderly and cardiovascular patients. Serotonin–norepinephrine reuptake inhibitors, particularly venlafaxine, carry a greater risk of hypertension, possibly related to greater effects on the sympathetic nervous system. The norepinephrine reuptake inhibitor reboxetine is considered a safe option because of its neutral effects on blood pressure in long-term studies, even if both hypotensive and hypertensive effects are reported. The dopamine–norepinephrine reuptake inhibitor bupropion can lead to blood pressure increases, usually at high doses, but may also cause orthostatic hypotension, especially in patients with cardiovascular diseases. The norepinephrine–serotonin modulators, mirtazapine and mianserin, have minimal effects on blood pressure but may rarely lead to orthostatic hypotension and falls. These adverse effects are also observed with the serotonin-reuptake modulators, nefazodone and trazodone, but seldomly with vortioxetine and vilazodone. Agomelatine, the only melatonergic antidepressant drug, may also have limited effects on blood pressure. Tricyclic antidepressants have been associated with increases in blood pressure, as well as orthostatic hypotension, particularly imipramine. Oral monoamine–oxidase inhibitors, less frequently skin patch formulations, have been associated with orthostatic hypotension or, conversely, with hypertensive crisis due to ingestion of tyramine-containing food (i.e., cheese reaction). Lastly, a hypertensive crisis may complicate antidepressant treatment as a part of the serotonin syndrome, also including neuromuscular, cognitive, and autonomic dysfunctions. Clinicians treating depressive patients should carefully consider their blood pressure status and cardiovascular comorbidities because of the effects of antidepressant drugs on blood pressure profiles and potential interactions with antihypertensive treatments.

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Section: Methodsmentioning

confidence: 94%

Antidepressant Drugs Effects on Blood Pressure

Calvi

Fischetti

Verzicco

et al. 2021

Front. Cardiovasc. Med.

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“…This interaction with σ1-receptors in the medulla may contribute to the sedative effect ( 24 ). Decreased systolic BP has been reported in σ1-receptor agonist therapy, suggesting another potential mechanism by which chlorpromazine modifies BP ( 25 ). Most importantly, PHEO cells secrete excess catecholamine, predominantly norepinephrine, and activate the α 1 -receptor, causing vasoconstriction that leads to serious hypertension ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

Chlorpromazine Efficiently Treats the Crisis of Pheochromocytoma: Four Case Reports and Literature Review

Wang

Yang

et al. 2021

Front. Cardiovasc. Med.

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Pheochromocytoma multisystem crisis (PMC) is a potentially lethal emergency due to catecholamine secretion. The condition manifests as severe hypertension to intractable cardiogenic shock and has a high mortality rate. This study explored the efficacy and safety of applying chlorpromazine on PMC patients. The study included seven patients (median age, 42 years; range, 14–57 years) diagnosed with pheochromocytoma. Four consecutive PMC patients were admitted to our critical care unit between 2016 and 2020 due to abdominal or waist pain, nausea, and vomiting. Their blood pressure (BP) fluctuated between 200–330/120–200 and 40–70/30–50 mmHg. Chlorpromazine (25 or 50 mg) was injected intramuscularly, followed by continuous intravenous infusion (2–8 mg/h). The patients' BP decreased to 100–150/60–100 mmHg within 1–3 h and stabilized within 3–5 days. Two weeks later, surgical tumor resection was successfully performed in all four patients. Similar clinical outcomes were also obtained in three patients with sporadic PMC reported in the literature who received chlorpromazine treatment, which reduced their BP readings from >200/100 mmHg to 120/70 mmHg. Our observations, combined with sporadic reports, showed that chlorpromazine efficiently controlled PMC. Thus, future studies on the use of chlorpromazine are warranted.

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