Inibição da corrente de cálcio tipo L por tramadol e enantiômeros em miócitos cardíacos de ratos

Medei, Emiliano; Raimundo, Juliana Montani; Nascimento, José; Trachez, Margarete M.; Sudo, Roberto T.; Zapata‐Sudo, Gisele

doi:10.1590/s0066-782x2011005000091

Cited by 6 publications

(1 citation statement)

References 26 publications

(27 reference statements)

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“…This suggests that tramadol may not reduce hERG current in cardiomyocytes or that our used concentrations of tramadol may have been insufficient to influence AP repolarization. An alternative explanation is that a reduction in outward hERG current is counterbalanced by reduced inward I Na (this study and Bok et al 36 ) and l -type Ca 2+ current, 57 culminating in no net change in AP duration. We also found no significant effect of tramadol on RMP, suggesting that I K1 is largely unaltered.…”

Section: Discussionmentioning

confidence: 60%

The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells

et al. 2023

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Background and aims Opioids are associated with increased risk of sudden cardiac death. This may be due to their effects on the cardiac sodium channel (Nav1.5) current. In the present study, we establish whether tramadol, fentanyl, or codeine affect Nav1.5 current. Methods Using whole-cell patch-clamp methodology, we studied the effects of tramadol, fentanyl, and codeine on currents of human Nav1.5 channels stably expressed in HEK293 cells, and on action potential (AP) properties of freshly isolated rabbit ventricular cardiomyocytes. Results In fully-available Nav1.5 channels (holding potential –120 mV), tramadol exhibited inhibitory effects on Nav1.5 current in a concentration-dependent manner with an IC50 of 378.5 ± 33.2 μM. In addition, tramadol caused a hyperpolarizing shift of voltage-gated (in)activation, and a delay in recovery from inactivation. These blocking effects occurred at lower concentrations in partially inactivated Nav1.5 channels: during partial fast-inactivation (close-to-physiological holding potential –90 mV), IC50 of Nav1.5 block was 4.5 ± 1.1 μM, while it was 16 ± 4.8 μM during partial slow-inactivation. The tramadol-induced changes on Nav1.5 properties were reflected by a reduction in AP upstroke velocity in a frequency-dependent manner. Fentanyl and codeine had no effect on Nav1.5 current, even when tested at lethal concentrations. Conclusion Tramadol reduces Nav1.5 currents, in particular, at close-to-physiological membrane potentials. Fentanyl and codeine have no effects on Nav1.5 current.

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Section: Discussionmentioning

confidence: 60%

The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells

et al. 2023

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Effect of Tramadol on Rabbit Uterine Contractile Activity Induced in Late Pregnancy

et al. 2017

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Effect of Tramadol infusion (5 mg/ml) on oxytocin-induced uterine contractile activity was studied in chronic experiment on female rabbits with different degrees of biological readiness for parturition. In case of sufficient biological readiness for parturition, Tramadol did not change the number of uterine contractions, but increased the amplitude and duration of each contraction against the background of increased creatine phosphate consumption by the myometrium. At the same time, Tramadol infusion to females without biological readiness for partirition suppressed induced uterine contractile activity by reducing the amplitude of each uterine contraction.

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A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment

et al. 2021

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Aims As an analgesic that acts upon the central nervous system (CNS), tramadol has gained popularity in treating moderate to severe pain. Recently, it has been increasingly reported as a drug of misuse with intentional overdoses or intoxications. This review focuses on tramadol intoxication in humans and its effects on different systems. Subject and method This narrative review provides a comprehensive view of the pharmacokinetics, mechanism of action, and incidence of tramadol toxicity with an in-depth look at its side effects. In addition, the main approaches to the management of tramadol poisoning are described. Results Tramadol poisoning can affect multiple organ systems: gastrointestinal, central nervous system (seizure, CNS depression, low-grade coma, anxiety, and over time anoxic brain damage), cardiovascular system (palpitation, mild hypertension to life-threatening complications such as cardiopulmonary arrest), respiratory system, renal system (renal failure with higher doses of tramadol intoxication), musculoskeletal system (rhabdomyolysis), endocrine system (hypoglycemia), as well as, cause serotonin syndrome. Seizure, a serious nervous disturbance, is more common in tramadol intoxication than with other opioids. Fatal tramadol intoxications are uncommon, except in ingestion cases concurrent with other medications, particularly CNS depressants, most commonly benzodiazepines, and ethanol. Conclusion With the increasing popularity of tramadol, physicians must be aware of its adverse effects, substantial abuse potential, and drug interactions, to weigh its risk–benefit ratio for pain management. Alternative therapies might be considered in patients with a previous overdose history to reduce risks for adverse outcomes.

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Inibição da corrente de cálcio tipo L por tramadol e enantiômeros em miócitos cardíacos de ratos

Cited by 6 publications

References 26 publications

The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells

The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells

Effect of Tramadol on Rabbit Uterine Contractile Activity Induced in Late Pregnancy

A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment

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