ALPHA(2)-ADRENOCEPTOR ANTAGONISM MAY CONTRIBUTE TO THE ATYPICAL PROPERTIES OF RISPERIDONE - EXPERIMENTAL SUPPORT FOR THE NUTT CASE

The therapeutic efficacy and reduction in side effects claimed for new antischizophrenic drugs such as clozapine and risperidone have been a scribed to their heightened affinity for serotonin 5-HT2 receptors rat her than D-2 receptors. A case for alpha(2)-adrenoreceptor antagonism has recently been argued. We have confirmed that at least one atypical property of risperidone (a rapid decrement in its ability to depress self-stimulation) can be partly prevented by an crz-adrenoreceptor ago nist (clonidine) but not by a 5-HT2 receptor agonist (DOI). This resul t supports the suggested role of alpha(2)-adrenoreceptor antagonism in counteracting extrapyramidal effects during treatment with risperidon e.