Evidence for low brain penetration by the H1-receptor antagonist temelastine (SK&F 93944)

Competition by the potent selective H1-receptor antagonist temelastine (SK & F 93944) with [3H]mepyramine binding to mouse cortex H1-receptors has been measured in vitro and vivo. The data were compared with that obtained using the classical H1-receptor antagonists mepyramine and promethazine and indicated that temelastine has relatively low ability to penetrate the blood-brain barrier compared with the latter two compounds. These studies also revealed that temelastine has relatively low affinity for mouse cortex H1-receptors compared with its affinity for H1-receptors in guinea-pig ileum and cortex, suggesting that it may be a useful compound with which to investigate potential H1-receptor tissue and species-related differences.