(+)-[ 3H]SKF 10,047, (+)-[ 3H]ethylketocyclazocine, μ, κ, δ and phencyclidine binding sites in guinea pig brain membranes

Abstract

Binding of the opiates (+)-[ 3H]SKF 10,047 [N-allylnormetazocine; (+)-[ 3H]SKF] and (+)-[ 3H]ethylketocyclazocine [(+)-[ 3H]EKC] were compared to μ, κ and δ and phencyclidine (PCP) receptor binding in guinea pig brain membranes. (+)-[ 3H]SKF and (+)-[ 3H]EKC binding were not blocked by naloxone, and had different drug selectivity compared to μ, κ and δ binding sites. The number of binding sites, drug selectivity and region distribution in brain were similar for (+)-[ 3H]SKF and (+)-[ 3H]EKC. Sigma opiates that are associated with psychotomimetic activities, such as pentazocine, cyclazocine, SKF 10,047 and bremazocine, were potent inhibitors of (+)-[ 3H]SKF and (+)-[ 3H]EKC binding. Haloperidol was the most potent inhibitor of (+)-[ 3H]SKF binding. Haloperidol and σ opiates demonstrated biphasic displacement of [ 3H]PCP binding, suggesting that [ 3H]PCP labelled two sites. PCP had a similar affinity for both (+)-[ 3H]SKF and [ 3H]PCP binding sites in the presence of 100 mM NaCl. The highest concentrations of (+)-[ 3H]SKF and (+)-[ 3H]EKC bindings sites were in the hypothalamus, anterior pituitary, midbrain, pons and medulla.