Method for preventing neurotoxic side effects of NMDA antagonists

摘要

This invention involves a method for reducing neurotoxic side effects that can be caused when NMDA antagonists such as MK-801 are used as anti- convulsants, to prevent excitotoxic damage in the central nervous system, or for anesthetic purposes in human or veterinary medicine. This method involves the use of anti-cholinergic agents such as scopolamine, atropine, benztropine, trihexyphenidyl, biperiden, procyclidine, benactyzine, or diphenhydramine in conjunction with, or subsequent to, administration of an NMDA antagonist. These anti- cholinergic agents greatly reduce or eliminate the deleterious side effects that can accompany NMDA antagonists (such as convulsion potentiating effects, as well as vacuole formation, mitochondrial dissolution, and possible death of cingulate/retrosplenial cerebrocortical neurons), without interfering with the useful properties of the NMDA antagonists. The protective agents described herein may also reduce the neurotoxic, psychotoxic, and/or hallucinatory side effects associated with illegal use of drugs such as phencyclidine.P PThis invention also relates to mixtures of NMDA antagonists and anti- cholinergic agents. Such mixtures can be used for beneficial purposes, such as providing safe anesthesia or ameliorating neurological disease processes, while also preventing deleterious side effects that might otherwise be caused by the NMDA antagonists.