Exocytosis mechanism as a new targeting site for mechanisms of action of antiepileptic drugs

Different Mechanisms Underlying the Antiepileptic and Antiparkinsonian Effects of Zonisamide

“…Both systemic administration of therapeutically-relevant dose and local perfusion of therapeuticallyrelevant concentration of ZNS increased and decreased the basal and depolarizationinduced releases of GABA in the hippocampus and frontal cortex, respectively (Okada et al, 1998;Yamamura et al, 2009a;Yamamura et al, 2009b;Yamamura et al, 2009c;. Furthermore, the inhibitory interneurons release GABA (Hirose et al, 2000;Okada et al, 2002;Staley et al, 1995;Zhu et al, 2008).…”

“…Systemic administration of ZNS affects monoamine release in the hippocampus, frontal cortex and striatum in a biphasic dose-dependent manner Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Okada et al, 2002). At therapeutically-relevant dose, ZNS increases extracellular levels of monoamines, whereas ZNS at supra-therapeutic dose decreases monoamine release Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Okada et al, 2002).…”

“…The generation of epileptic seizures could be due to a relative imbalance between excitatory and inhibitory neurotransmission, resulting in increased neuronal excitability and abnormally frequent patterns of discharge (Hirose et al, 2000;Okada et al, 2002). Glutamate is one of the main excitatory neurotransmitters, and excessive release of glutamate seems to precipitate seizures in epileptic patients and in animal models of epilepsy (Hirose et al, 2000;Okada et al, 2002).…”

“…Glutamate is one of the main excitatory neurotransmitters, and excessive release of glutamate seems to precipitate seizures in epileptic patients and in animal models of epilepsy (Hirose et al, 2000;Okada et al, 2002). In contrast to glutamate, various other neurotransmitters, e.g., GABA, dopamine, serotonin and acetylcholine, are involve in the regulation of inhibitory transmission (Hirose et al, 2000;Okada et al, 2002;Okada et al, 2010).…”

“…At therapeutically-relevant dose, ZNS increases extracellular levels of monoamines, whereas ZNS at supra-therapeutic dose decreases monoamine release Murakami et al, 2001;Okada et al, 1999;Okada et al, 1992;Okada et al, 1995;Okada et al, 2002). Similar to its effect on the release of monoamines, both acute and chronic administration of therapeutically-relevant doses of ZNS enhance the turnover of dopamine and serotonin (i.e., monoamine synthesis) Okada et al, 1992;Okada et al, 1995).…”