A class of quinolinic sulfide derivatives of formula I are potent and specific antagonists at the strychnine insensitive glycine bitding site on the NMDA receptor complex with an pharmacological advantageous profile. They may be useful in treatment or prevention of neuro-degenerative disorders. Particularly, the compounds included in the present invention are especially useful for minimizing damage of the central nervous system arising as a consequence of ischemic or hypoxic condition such as stroke, hypoglycemia, cerebral ischemia, cardiac arrest, and physical trauma. They are also useful in prevention of chronic neurodegenerative disorders including epilepsy, Alzheimer's disease, Huntington's disease and Parkinsonism. By virtue of their NMDA receptor antagonist properties, the present compounds may also use as anticonvulsant, analgesic, antidepressant, anxiolytic, and antischizophrenic agent. Formula I ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R are defined in specification.