MILTIRONE, A CENTRAL BENZODIAZEPINE RECEPTOR PARTIAL AGONIST FROM A CHINESE MEDICINAL HERB SALVIA-MILTIORRHIZA

Ten diterpene quinones, which inhibited the binding of [H-3]flunitrazepam to central benzodiazepine receptors with IC50s ranging from 0.3 to 36.2-mu-M, were isolated from the ethereal extract of the roots of Salvia miltiorrhiza. Among these natural products, miltirone has the highest potency (IC50 = 0.3-mu-M). It was orally active in an animal model used to predict clinical tranquilizing effects. Unlike diazepam, miltirone behaved as a partial agonist in the central benzodiazepine receptor binding and behavioural tests. Moreover, it produced no acute muscle relaxant effect and did not induce drug dependence and withdrawal reactions after chronic administration in mice.