Unmasking hidden risks: The surprising link between PDE5 inhibitors and seizure susceptibility.

Autor: Silva ALMD; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Nascimento CP; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Azevedo JEC; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Vieira LR; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Hamoy AO; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Tiago ACDS; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Martins Rodrigues JC; Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., de Araujo DB; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Favacho Lopes DC; Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., de Mello VJ; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil., Hamoy M; Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, UFPA, Belém, Pará, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Nov 30; Vol. 18 (11), pp. e0294754. Date of Electronic Publication: 2023 Nov 30 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0294754
Abstrakt: Background: Phosphodiesterase 5 inhibitors (PDE5i) are the first line treatment for erectile dysfunction; however, several articles and case reports have shown central nervous system effects, that can cause seizures in susceptible patients. This study aims to describe the changes caused by the use of Sildenafil and Tadalafil through the analysis of abnormalities expressed in the electrocorticogram (ECoG) of rats and evaluate the seizure threshold response and treatment of seizures with anticonvulsants.
Materials and Methods: The study used 108 rats (Wistar). Before surgery for electrode placement in dura mater, the animals were randomly separated into 3 experiments for electrocorticogram analysis. Experiment 1: ECoG response to using PD5i (Sildenafil 20mg/kg and Tadalafil 2.6mg/kg p.o.). Experiment 2: ECoG response to the use of PD5i in association with Pentylenetetrazole (PTZ-30 mg/kg i.p.), a convulsive model. Experiment 3: ECoG response to anticonvulsant treatment (Phenytoin, Phenobarbital and Diazepam) of seizures induced by association IPDE5 + PTZ. All recordings were made thirty minutes after administration of the medication and analyzed for ten minutes, only once. We considered statistical significance level of *p<0.05, **p<0.01 and ***p < 0.001.
Results: After administration of Sildenafil and Tadalafil, there were increases in the power of recordings in the frequency bands in oscillations in alpha (p = 0.0920) and beta (p = 0.602) when compared to the control group (p<0.001). After the use of Sildenafil and Tadalafil associated with PTZ, greater potency was observed in the recordings during seizures (p<0.001), however, the Sildenafil group showed greater potency when compared to Tadalafil (p<0.05). Phenobarbital and Diazepam showed a better response in controlling discharges triggered by the association between proconvulsant drugs.
Conclusions: PDE5i altered the ECoG recordings in the rats' motor cortexes, demonstrating cerebral asynchrony and potentiating the action of PTZ. These findings demonstrate that PDE5i can lower the seizure threshold.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje