Pharmacological identification of SM-21, the novel sigma(2) antagonist

SM-21 is a tropane analogue with high affinity and selectivity for sigma (2 ) receptor subtype. In the absence of highly selective sigma (2) antagonist s, the aim of the present study was to determine whether SM-21 is endowed w ith antagonistic activity. The experiments were conducted in rats by induci ng neck dystonia, which is reported to be subsequent to activation of sigma (2) receptors. SM-21 (10 nmol/0.5 mul) was able to prevent torsion of the neck obtained by administration of the sigma (1)-sigma (2) agonist 1,3-di-( 2-tolyl)guanidine (DTG, 5 nmol/0.5 mul) in the red nucleus. These data indi cate that SM-21 is a potent and selective sigma (2) antagonist. (C) 2000 El sevier Science Inc. All rights reserved.