Einführung und Wirkmechanismen

Zusammenfassung

Zonisamid (ZNS) ist ein Benzisoxazolderivat, das sich strukturell von bisher zugelassenen antiepileptisch wirksamen Substanzen unterscheidet. Es besitzt multiple Wirkmechanismen, deren Bedeutung für die antikonvulsive Wirkung noch nicht vollständig geklärt ist. So unterbricht Zonisamid die synchronisierte neuronale Entladung durch direkte Effekte auf spannungsabhängige Natriumkanäle und T-Typ-Kalziumkanäle. Dadurch wird die Verbreitung von epileptischen Entladungen reduziert und die epileptische Aktivität unterbunden. Zugleich besitzt Zonisamid eine modulatorische Wirkung auf die GABA-vermittelte neuronale Inhibition und es gibt Hinweise, dass die Substanz sowohl die dopaminerge und serotonerge Neurotransmission erleichtert als auch den Azetylcholinstoffwechsel beeinflusst. Auch eine Inhibition der exzitatorischen glutamatergen Transmission durch Reduktion der präsynaptischen Glutamatfreisetzung wurde beschrieben. Klinisch scheinen diese multiplen Wirkmechanismen mit einer breiten antikonvulsiven Wirksamkeit zu korrelieren.

Abstract

Zonisamide (ZNS) is a benzisoxazole derivate not structurally related to currently licensed antiepileptic drugs. It has multiple modes of action whose impact on the anticonvulsant effect is not yet fully understood: ZNS interrupts the synchronized neuronal firing through direct effects on voltage-dependent sodium and T-type calcium channels. Thus epileptiform propagation and activity are blocked. Furthermore ZNS has a modulating effect on the GABAergic inhibition, and may act on the dopaminergic and serotonergic neurotransmission and on acetylcholine pathways. An inhibition of excitatory glutamatergic transmission by reduction of the presynaptic release of glutamate has been also described. These modes of action suggest a broad anticonvulsant efficacy.

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