Compounds, composition and method for ameliorating alcohol or drug dependency
withdrawal syndromes and withdrawal-induced brain damage are disclosed. In particular,
a series of N-substituted-4-uredo-5,7-dihalo-2-carboxy quinoline compounds are
disclosed having combined properties as antagonists of voltage-sensitive sodium
channels (VSNaC) and as selective competitive antagonists at the strychnine-intensive
glycine site of N-methyl-D-aspartate (NMDA) receptors. The disclosed compounds
prevent or reduce the signs and symptoms of neurohyperexcitability and particularly
the neurohyperexcitability associated with withdrawal syndrome manifested by patients
upon withdrawal from chronic use of dependence inducing agents (e.g. ethanol, barbiturates,
opiates etc.). The combined actions of the disclosed compound on VSNaC and NMDA
receptors also impart properties to these compounds that are important in preventing
and reducing excitotoxic neurodegeneration and reducing anxiety without the undesirable
CNS depressant side-effects of agents hitherto employed for these purposes.