The effect of benzodiazepines and flumazenil on motor cortical excitability in the human brain

In the present study, the effects of benzodiazepines (diazepam) were evalua ted in terms of cortical excitability changes, as tested with transcranial magnetic simulation (TMS). In particular, analyzed were drug-induced change s regarding two selected parameters of TMS: (1) the cortical excitability t hreshold and (2) the silent period duration (SP). For this purpose, we eval uated the effects of long-term therapy with diazepam in the patients affect ed by anxiety disorders and the changes induced by single oral doses of dia zepam in both healthy controls and patients. In addition, we tested cortica l excitability changes in two 'extreme conditions' where a considerable con centration of serum benzodiazepine-like activity was reached, as represente d by diazepam overdose and idiopathic recurrent stupor (IRS). In both group s of patients, a significant increment of motor threshold was found, while in the overdose patients, the SP was also increased. The administration of flumazenil in these two conditions was followed by a prompt reversal effect , consisting of a return to normal cortical excitability parameters. The lo ng-term usage of diazepam in patients with anxiety disorders is associated with significantly increased threshold: the increased value of these parame ters was temporarily further enhanced by the administration of a single ora l dose of diazepam, which, in normal control subjects, is not associated wi th changes of cortical excitability. The results of this study reveal that different physio-pathological conditions induced by the influence of benzod iazepine and its antagonist are reflected in excitability changes which att est to the involvement and modification of cortical GABAergic activity. (C) 1999 Published by Elsevier Science B.V. All rights reserved.