PHARMACOLOGICAL IDENTIFICATION OF SM-21, THE NOVEL SIGMA2 ANTAGONIST

SM-21 is a tropane analogue with high affinity and selectivity for s2 receptor subtype. In the absence of highly selective s2 antagonists, the aim of the present study was to determine whether SM-21 is endowed with antagonistic activity. The experiments were conducted in rats by inducing neck dystonia, which is reported to be subsequent to activation of s2 receptors. SM-21 (10 nmol/0.5 ml) was able to prevent torsion of the neck obtained by administration of the s1±s2 agonist 1,3-di-(2-tolyl)guanidine (DTG, 5 nmol/0.5 ml) in the red nucleus. These data indicate that SM-21 is a potent and selective s2 antagonist.