2,4(1H)-Diarylimidazoles have been previously shown to inhibit hNaV1.2 sodium (Na) channel currents. Since many of the clinically used anticonvulsants are known to inhibit Na channels as an important mechanism of their action, these compounds were tested in two acute rodent seizure models for anticonvulsant activity (MES and scMet) and for sedative and ataxic side effects. Compounds exhibiting antiepileptic activity were further tested to establish a dose response curve (ED50). The experimental data identified four compounds with anticonvulsant activity in the MES acute seizure rodent model (compound 10, ED50 = 61.7 mg/kg; compound 13, ED50 = 46.8 mg/kg, compound 17, ED50 = 129.5 mg/kg and compound 20, ED50 = 136.7 mg/kg). Protective indexes (PI = TD50/ED50) ranged from 2.1 (compound 10) to greater than 3.6 (compounds 13, 17 and 20). All four compounds were shown to inhibit hNaV1.2 in a dose dependant manner. Even if a correlation between sodium channel inhibition and anticonvulsant activity was unclear, these studies identify four Na channel antagonists with anticonvulsant activity, providing evidence that these derivatives could be potential drug candidates for development as safe, new and effective antiepileptic drugs (AEDs).

Anticonvulsant Activity of 2,4(5)-Diarylimidazoles in Mice and Rat Models / Rivara, Mirko; M., Fantini; Zuliani, Valentina; M. K., Patel. - 34:(2009), pp. 103-103. (Intervento presentato al convegno Drugs of the Future tenutosi a Barcellona nel October, 4-6 2009).

Anticonvulsant Activity of 2,4(5)-Diarylimidazoles in Mice and Rat Models

RIVARA, Mirko;ZULIANI, Valentina;
2009-01-01

Abstract

2,4(1H)-Diarylimidazoles have been previously shown to inhibit hNaV1.2 sodium (Na) channel currents. Since many of the clinically used anticonvulsants are known to inhibit Na channels as an important mechanism of their action, these compounds were tested in two acute rodent seizure models for anticonvulsant activity (MES and scMet) and for sedative and ataxic side effects. Compounds exhibiting antiepileptic activity were further tested to establish a dose response curve (ED50). The experimental data identified four compounds with anticonvulsant activity in the MES acute seizure rodent model (compound 10, ED50 = 61.7 mg/kg; compound 13, ED50 = 46.8 mg/kg, compound 17, ED50 = 129.5 mg/kg and compound 20, ED50 = 136.7 mg/kg). Protective indexes (PI = TD50/ED50) ranged from 2.1 (compound 10) to greater than 3.6 (compounds 13, 17 and 20). All four compounds were shown to inhibit hNaV1.2 in a dose dependant manner. Even if a correlation between sodium channel inhibition and anticonvulsant activity was unclear, these studies identify four Na channel antagonists with anticonvulsant activity, providing evidence that these derivatives could be potential drug candidates for development as safe, new and effective antiepileptic drugs (AEDs).
2009
Anticonvulsant Activity of 2,4(5)-Diarylimidazoles in Mice and Rat Models / Rivara, Mirko; M., Fantini; Zuliani, Valentina; M. K., Patel. - 34:(2009), pp. 103-103. (Intervento presentato al convegno Drugs of the Future tenutosi a Barcellona nel October, 4-6 2009).
File in questo prodotto:
File Dimensione Formato  
Zuliani.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 21.5 kB
Formato Adobe PDF
21.5 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
ABSTRACT.pdf

non disponibili

Tipologia: Abstract
Licenza: Creative commons
Dimensione 10.08 kB
Formato Adobe PDF
10.08 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2327803
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact