Evaluation of the role of different neurotransmission systems in the anticonvulsant action of sildenafil in the 6 Hz-induced psychomotor seizure threshold test in mice.

Abstract

Sildenafil influences seizure activity in animal seizure models, and its both proconvulsant and anticonvulsant effects were reported. We previously found that this PDE5 inhibitor significantly increased seizure threshold for the 6 Hz-induced psychomotor seizures in mice and therefore we aimed to investigate the influence of some modulators of neurotransmitter receptors, i.e., diazepam (GABA/benzodiazepine receptor agonist), flumazenil (GABA/benzodiazepine receptor antagonist), N-methyl-d-aspartic acid (NMDA glutamate receptor agonist), CGP 37849 (NMDA receptor antagonist), metergoline (serotonin receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (adenosine A1 receptor antagonist) and β-funaltrexamine (μ opioid receptor antagonist), on the anticonvulsant effect of sildenafil in this test. Additionally, we estimated influence of the studied compounds and their combinations with sildenafil on the muscular strength (assessed in the grip strength test) and motor coordination (assessed in the chimney test) in mice. Our results indicate that anticonvulsant properties of sildenafil in the 6 Hz test in mice might be related to its interactions with the GABAergic, glutamatergic, serotonergic and adenosinergic neurotransmission. We did not find interactions between sildenafil and μ opioid receptors. Neither the studied ligands nor their combinations with sildenafil impaired muscular strength and motor coordination. In conclusion, sildenafil has complex and extensive influence on neurotransmission and seizure generation in the CNS.

• Authors: Dorota Nieoczym, Katarzyna Socała, Piotr Wlaź
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 107 Pg. 1674-1681 (Nov 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 30257385 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anticonvulsants
• Phosphodiesterase 5 Inhibitors
• Sildenafil Citrate

Topics

• Animals
• Anticonvulsants (administration & dosage, pharmacology)
• Disease Models, Animal
• Electroshock (adverse effects)
• Male
• Mice
• Muscle Strength (drug effects)
• Phosphodiesterase 5 Inhibitors (administration & dosage, pharmacology)
• Seizures (drug therapy, physiopathology)
• Sildenafil Citrate (administration & dosage, pharmacology)
• Synaptic Transmission (drug effects)