Alcobra Says MG01CI No Effect on Dopamine/Noradrenaline Targets

Alcobra Ltd. (Nasdaq: ADHD)(the "Company"), an emerging biopharmaceutical company primarily focused onthe development and commercialization of its proprietary drug, MG01CI(Metadoxine extended-release), to treat cognitive dysfunctions, such as ADHDand Fragile X Syndrome, announced today the results from a series ofpreclinical studies that evaluated the mechanism of action of MG01CI. MG01CIis composed of a dual-release formulation of Metadoxine that providesimmediate as well as extended-release formulations in a single oral dose."These studies shed important light on the novel mechanism of action and theunique effects that MG01CI may have in treating cognitive dysfunctions,"commented Dr. Yaron Daniely, President and CEO of Alcobra Ltd. "MG01CI appearsto enhance the ability of cells to correct abnormal signaling pathways thatmay be involved with cognitive impairment, while not increasing levels ofneurotransmitters in the brain such as dopamine, norepinephrine and serotonin.We believe these findings might account for the improved effect on attentionas well as the favorable tolerability profile that we have observed thus farin clinical trials with MG01CI."The studies showed that Metadoxine is a selective antagonist to the 5-HT2Breceptor, a member of the serotonin receptor family. Importantly, Metadoxinedid not show any binding to other serotonin receptors, and did not bind thecharacterized targets of existing stimulant and non-stimulant medications(dopamine and norepinephrine receptors and transporters). In accordance withthese findings, Metadoxine did not affect the concentration of theseneurotransmitters or their metabolites in the brain.Metadoxine treatment affected several specific molecular targets residinginside the cell in a dose-dependent manner, including critical signalingmodulators such as the proteins Akt and Extracellular signal-related Kinase(ERK), but did not affect other targets such as cyclic AMP (cAMP) and ProteinKinase A (PKA). In a preclinical Fragile X disease model, elevated levels ofAkt and ERK were normalized (reduced) by Metadoxine, while levels of the GSTprotein were increased. Electrophysiological studies also showed thatMetadoxine caused a dose-dependent, reversible reduction in glutamatergicexcitatory transmission and enhancement of GABAergic inhibitory transmission,changes that may be associated with cognitive regulation."Our findings to date suggest a distinct mechanism of action for Metadoxine intreating cognitive disorders such as ADHD and Fragile X Syndrome," added Dr.Jonathan Rubin, Chief Medical Officer of Alcobra Ltd. "We are eager to moveforward with additional clinical trials in these populations as we learn moreabout the differentiated characteristics of our product."