Mesulergine, a selective serotonin-2 ligand in the rat cortex, does not label these receptors in porcine and human cortex: evidence for species differences in brain serotonin-2 receptors

The kinetic and pharmacological characteristics of the binding of 3H]ketanserin and 3H]mesulergine to frontal cortical brain membranes from rat, pig and human were studied. In the 3 species 3H]ketanserin labeled sites with the characteristics of the 5-HT2 receptors previously described in the rat. In contrast, 3H]mesulergine labeled 5-HT2 receptors in rat, but not in pig and human cortices. The characteristics of the sites labeled by 3H]mesulergine in pig cortex were similar to those of sites in the choroid plexus of rats, pigs and humans. While several reputed 5-HT2 ligands presented a similar affinity for the 3H]ketanserin binding sites in the 3 species, other such ligands, e.g. mesulergine, methysergide, cinanserin and LSD which displaced these sites with high affinity in rat brain, had lower affinities in pig and human brain. These results indicate that 5-HT2 receptors show different pharmacological profiles in different species. Caution should thus be exerted in extrapolating data from laboratory animals to humans.