Barbiturates as safening agents in conjunction with NMDA antagonists
OwnerJohn W. Olneyinventor
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Abstract
Certain barbiturates have been shown to completely prevent the neurotoxic injury to cerebrocortical neurons that can be caused by NMDA antagonists. The use of barbiturates as "safening agents" allows NMDA antagonists (including powerful NMDA antagonists such as MK-801) to be used safely as neuroprotectants to prevent brain damage due to hypoxia/ischemia caused by strokes, cardiac arrest, perinatal asphyxia, and various other conditions.
Claims16
A composition of matter, comprising a mixture of an NMDA antagonist and a barbiturate, wherein the NMDA antagonist is present in a dosage that can protect central nervous system neurons against excitotoxic neuronal death, and wherein the barbiturate acts as a direct GABA agonist and is present in an effective dosage that can prevent vacuole formation and induction of heat shock proteins in cingulate or retrosplenial cortical neurons which would be caused by administration of the NMDA antagonist without the barbiturate.
A method for preventing NMDA antagonists from generating vacuoles or inducing heat shock protein expression in cingulate or retrosplenial cortical neurons, comprising the step of administering to a susceptible mammal, in conjunction with an NMDA antagonist capable of causing vacuole formation or inducing heat shock protein expression in cingulate or retrosplenial cortical neurons, a therapeutically effective amount of a barbiturate which acts as a direct agonist of gamma-aminobutyric acid at gamma-aminobutyric acid/benzodiazepine receptors in the central nervous system.
In the method of using an NMDA antagonist to reduce hypoxic or ischemic damage to a mammalian central nervous system, the improvement consisting of co-administering, along with an NMDA antagonist which reduces hypoxic or ischemic damage but which also causes neurotoxic side effects, a therapeutically effective quantity of a second pharmaceutical agent comprising a barbiturate which acts at gamma-amino-butyric acid receptors and which prevents neurotoxic side effects of NMDA antagonists.
Dependencies are inferred from the claim text.