[ 3H]Mr 2034 labels a high affinity opioid κ-receptor not accessible to naloxazone

Saturation binding studies with [ 3H]Mr 2034, an opioid κ-agonist, were carried out using brain homogenates from naloxazone-pretreated rats (200 mg/kg subcutaneously 16 hours before killing). [ 3H]Mr 2034 showed unaffected binding characteristics, compared to membrane homogenates of untreated controls. However, in contrast to this finding, naloxazone blocked the high affinity binding of other tritiated opioid agonists and antagonists, among them the κ-agonist [ 3H]ethylketocyclazocine. Displacement studies with [ 3H]dihydromorphine, [ 3H]ethylketocyclazocine and [ 3H]Mr 2034 in brain membrane homogenates from untreated rats and using various opioid agonists and antagonists indicated that these substances are capable of differentiating between the two κ-ligands [ 3H]ethylketocyclazocine and [ 3H]Mr 2034, too.