This invention discloses mixtures of NMDA antagonists and anti-cholinergic agents, which can be used to prevent excitotoxic damage in the central nervous system or for anesthetic purposes in human or veterinary medicine. Anti-cholinergic agents such as scopolamine, atropine, benztropine, trihexyphenidyl, biperiden, procyclidine, benactyzine, or diphenhydramine can be used in conjunction with, or subsequent to, administration of an NMDA antagonist such as MK-801. The NMDA antagonist exerts a primary protective effect by preventing or reducing excitotoxic damage due to stroke, perinatal asphyxia, and various other types of injury or disease; however, strong NMDA antagonists such as MK-801 can also cause neurotoxic side effects, including vacuole formation, mitochondrial dissolution, and neuronal death in certain types of neurons such as cingulate/retrosplenial cerebrocortical neurons. The anti-cholinergic agent will reduce or eliminate those damaging side effects, without interfering with the primary protective value of the NMDA antagonist. The anti-cholinergic agents described herein can also reduce the toxic side effects associated with illegal use of drugs such as phencyclidine (also known as PCP or angel dust).

Pharmacological composition for preventing neurotoxic side effects of NMDA antagonists

The present invention provides compositions and methods for preventing, treating or reversing neuronal dysfunction in a mammal resulting from exposure to organophosphate nerve agents, organophosphate insecticides and incapacitating agents of the central nervous system (CNS); CNS injury, including traumatic brain injury, neurologic complications of cardiac surgery, perinatal asphyxia, and stroke, spinal cord injury, and peripheral nerve injury; and neuronal disorders associated with the loss of motor function including post-polio syndrome, amyotrophic lateral sclerosis, myasthenia gravis, Parkinson's disease and Rett syndrome; neurodegenerative disorders including Alzheimer's disease, mild cognitive impairment and schizophrenia; and cognitive impairment associated with aging. The compositions of the invention preferably comprise in effective amounts (a) at least one acetylcholinesterase inhibitor, (b) at least one compound with anticholinergic properties or both anticholinergic and antiglutamatergic properties, (c) optionally an anticonvulsive compound, and a pharmaceutically acceptable carrier.

anticholinergic/accident vascular cerebral

Pharmacological composition for preventing neurotoxic side effects of NMDA antagonists

Pharmaceutical compositions and methods for preventing, treating, or reversing neuronal dysfunction

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