The Effects of Riluzole on Cisplatin-induced Ototoxicity

Abstract Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzolemay have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.

Glutamate modulators as novel interventions for mood disorders

Recentes evidências sugerem que as moléculas críticas nas cascatas de sinalizacão neurotrófica são alvos de longo prazo dos antidepressivos monoaminérgicos disponíveis atualmente. Na medida em que transtornos graves e crônicos são caracterizados por deficiências na resiliência neuronal, estratégias farmacológicas que sejam úteis para uma funcão neuroprotetora talvez possam alterar a fisiopatologia e modificar a progressão da doenca. Vários enfoques promissores envolvem a modulacão do sistema neurotransmissor do glutamato, via bloqueio ou potencializacão do receptor pós-sináptico e inibicão da liberacão vesicular pré-sináptica. Foi realizada uma revisão focada da literatura científica existente, com a discussão de três compostos ou classes de drogas que estão atualmente sob investigacão clínica: a ketamina, o riluzol e os potencializadores de receptores de AMPA. DISCUSSAO: Estudos recentes com pacientes com transtornos de humor sugerem que a ketamina, um antagonista do receptor NMDA, poderia ter demonstrado propriedades antidepressivas rápidas. O riluzol demonstrou reverter deficiências mediadas pelo glutamato na plasticidade neuronal e estimular a síntese de fatores neurotróficos derivados do cérebro. Ensaios abertos com depressão resistente ao tratamento produziram resultados promissores. Da mesma forma, os potencializadores de receptores de AMPA impactam favoravelmente os fatores neurotróficos, assim como melhoram a cognicão. CONCLUSÕES: Enfoques farmacológicos que modulam os componentes do sistema de glutamato oferecem novos alvos para transtornos de humor recorrentes e graves. São necessários estudos controlados.

Current and new strategies in therapy of neurodegenerative disorders: amyotrophic lateral sclerosis as a model

For years researchers have known that free radicals can cause cell degeneration, especially in the brain, so there is a role for the oxidative stress and free radicals in the chronic neurodegenerative disorders. Riluzole is recommended for improving the prognosis of patients suffering from the neurodegenerative disorder, Amyotrophic lateral sclerosis [ALS], and it thought to be acting as nueroprotective agent by the inhibition of glutamatergic transmission in the CNS. The familial [ALS], has been mapped to chromosome 2q33 and aldehyde oxidise enzyme has been mapped also with the same gene 2q33. So it noteworthy to make a link between Riluzol and aldehyde oxidase and the possible interaction between them in the CNS, which may contribute to the neuroprotective effect of Riluzole by inhibiting ROS production or altering the balance between hydrogen peroxide [H[2]O[2]] and superoxide anion [O[2]]