Correlation between neuroleptic binding to σ1 and σ2 receptors and acute dystonic reactions

Acute dystonic reactions are motor side effects that occur soon after the initiation of neuroleptic treatment. Although earlier studies indicate that these abnormal movements can be induced in animals and humans via activation of a receptors, the relative contribution of the different sigma receptor subtypes is unknown. Since sigma(1) and sigma(2) receptor are differentially represented in motor regions of the brain, the affinities, of 17 neuroleptics for these sigma receptor subtypes were determined using competition binding studies. The results revealed that most neuroleptics do not exhibit selectivity for either of the a receptor subtypes, as reflected by a significant correlation between the affinities of the neuroleptics for sigma(1) vs. sigma(2) receptors. Moreover, when the sigma binding affinities of the neuroleptics were correlated with the tendency of the drugs to produce acute dystonic reactions in humans, then was a significant correlation for both subtypes. Together with earlier studies in animals, the data suggest that neuroleptic-induced motor side effects can be mediated through both sigma(1) and sigma(2) receptors. (C) 2000 Elsevier Science B.V. All rights reserved.