[H-3]YM-09151-2 (nemonapride), a potent radioligand for both sigma(1) and sigma(2) receptor subtypes

USING K+ phosphate buffer with 25 nM spiperone, [H-3]YM-09151-2 binding showed a high affinity for sigma receptors but no affinity for D-2 dopamine or 5-HT1A receptors in rat brain. The order of pK(i) values of various sigma compounds at [H-3]YM-09151-2 binding sites and stereoisomer selectivity were consistent with previous studies using other sigma ligands such as (+)-[H-3]SKF-10047, [H-3]DTG and (+)-[H-3]3-PPP. Although Scatchard analysis fitted a one-site model, competition between [H-3]YM-09151-2 and (+)-pentazocine revealed two sites, sigma(1) and sigma(2) receptors, at which the K-i values of YM-09151-2 were 8.4nM and 9.6nM, respectively. Autoradiography using [H-3]YM-09151-2 also showed a characteristic distribution of sigma receptors in rat brain. [H-3]YM-09151-2 is, therefore, a potent and useful radioligand for sigma(1)/sigma(2) receptor subtypes.