Correlation between neuroleptic binding to sigma(1) and sigma(2) receptorsand acute dystonic reactions

Acute dystonic reactions are motor side effects that occur soon after the i nitiation of neuroleptic treatment. Although earlier studies indicate that these abnormal movements can be induced in animals and humans via activatio n of a receptors, the relative contribution of the different sigma receptor subtypes is unknown. Since sigma(1) and sigma(2) receptor are differential ly represented in motor regions of the brain, the affinities, of 17 neurole ptics for these sigma receptor subtypes were determined using competition b inding studies. The results revealed that most neuroleptics do not exhibit selectivity for either of the a receptor subtypes, as reflected by a signif icant correlation between the affinities of the neuroleptics for sigma(1) v s. sigma(2) receptors. Moreover, when the sigma binding affinities of the n euroleptics 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 n euroleptic-induced motor side effects can be mediated through both sigma(1) and sigma(2) receptors. (C) 2000 Elsevier Science B.V. All rights reserved .