Use of alpha-2 adrenergic drugs to prevent adverse effects of NMDA receptor hypofunction (NRH)

摘要

Methods and compositions are disclosed for treating or preventing adverse CNS effects produced by NMDA receptor hypofunction (NRH), including hypofunction induced by NMDA antagonist drugs, and hypofunction occurring as a causative or aggravating factor in schizophrenia. One method of this invention comprises administering an alpha-2 adrenergic (. alpha.2) receptor agonist drug along with an NMDA antagonist drug. The NMDA antagonist drug exerts a primary benefit in reducing excitotoxic brain damage, alleviating neuropathic pain, or preventing or avoiding tolerance or addiction to various types of drugs. The &agr;2 agonist drug acts as a secondary or "safener" drug, to prevent the neurotoxic side effects that would be caused by the NMDA antagonist in the absence of the safener drug. Another method disclosed herein involves the use of an &agr;2 agonist drug, by itself, to combat a different and naturally- occurring form of NMDA receptor hypofunction which occurs as a causative or aggravating mechanism in people suffering from schizophrenia. Although &agr;2 agonists are usually not effective in treating long-standing cases of chronic schizophrenia, where pathological changes in the brain have already reached or approached maximal levels, &agr;2 agonists can be administered early in the illness, such as at the first signs of schizophrenic illness, and continuously or intermittently thereafter to prevent the development or worsening of pathological brain changes.