Use of 5HT-2A serotonin agonists to prevent adverse effects of NMDA receptor hypofunction

摘要

This invention relates to a new method for treating or preventing brain damage caused by NMDA receptor hypofunction (NR/hypo), using drugs such as lisuride which stimulate (agonize) activity at the 5HT-2A class of serotonin receptors, but which do not cause hallucinations. Data disclosed herein indicate that stimulation of both 5HT-2A and 5HT-2C receptors causes hallucinations, while stimulation of 5HT-2A receptors but not 5HT-2C receptors does not. Accordingly, to be useful herein, non- hallucinatory 5HT-2A agonists should either (1) antagonize (suppress) activity at 5HT-2C receptors, or (2) have no significant effect on activity at 5HT-2C receptors. Selective non- hallucinatory 5HT-2A agonists can be used in either of two treatment methods disclosed herein. P POne such treatment comprises administering a 5HT-2A receptor agonist as a "safener drug" which accompanies an NMDA antagonist drug that is being used for a therapeutic purpose.PPAnother method disclosed herein involves the use of a 5HT-2A agonist drug, by itself, to combat a naturally-occurring form of NMDA receptor hypofunction which occurs in people suffering from schizophrenia. Although 5HT-2A agonists would not be optimally effective in treating long-standing cases of chronic schizophrenia, where pathological changes in the brain have already reached maximal or severe levels, 5HT-2A agonists can be administered early in the illness, such as at the first signs of schizophrenic illness, and continuously thereafter to prevent the development or worsening of pathological brain dysfunction and the resulting psychosis.