(-)-Tetrahydropalmatine

DescriptionTetrahydropalmatine (THP) is an isoquinoline alkaloid found in in several different plant species, mainly in the Corydalis genus (Yan Hu Suo), but also in other plants such as Stephania rotunda (Qian Jin Teng). These plants exhibits analgesic, antinociceptive, anxiolytic, antidepressant, and anti-parasitic activities, and have traditional uses in Chinese herbal medicine. In particular, the levo isomer of THP (l-THP) appears to contribute to many of the therapeutic effects of these herbs. Notably, the dextro isomer of THP has distinct pharmacological actions that include depletion of monoamines and may contribute to the toxicology profile of THP-containing preparations or racemic mixtures of the compound. In addition to serving as an active constituent in traditional Chinese herbal preparations, purified or synthetic l-THP is approved for use and available as Rotundine or Rotundin in China, where l-THP has been used as an analgesic and sedative for more than 40 years.

DescriptionThe roots of Stephania rotunda furnish this alkaloid which forms colourless plates when crystallized from EtOH. It is laevorotatory with [α]23D - 262° (EtOH) and gives a crystalline hydrochloride with m.p. 258-9°C (dec.) and the methiodide which decomposes at that same temperature. Three methoxyl groups and one methyl group are present.

HistoryFrom the 1920s, many researchers have focused on the alkaloid compounds contained in the Yan Hu Suo and extracted more than 30 different kinds of alkaloids. Among them Rotundine is one of the most important active compounds and has been successfully applied in clinical practice.Tetrahydropalmatine (THP) was firstly discovered by Zhao Chenggu, a famous medicinal phytochemist in China. He isolated 13 kinds of alkaloids and identified the structure of 6 of them. In 1936, Huang Minglong, a famous organic chemist, proved THP is a racemate. From 1933, Wang Jingxi and Lu Zihui began to study the pharmacological effects of THP and found that THP could induce catalepsy in animals. Rotundine is a levo-THP and obtained from the resolution of DL-THP during 1959–1964. From 1956 to 1965, the famous Chinese neuropharmacologist, Jin Guozhang, identified Rotundine as the main effective component in Yan Hu Suo and further studied its underlying mechanisms. He also found that Stephania contains abundant L-THP, which could become the source of clinical medication.In 1965, Rotundine was recorded in the textbooks of pharmacology. After over 20years of clinical practices, people have proved that Rotundine has reliable efficacy and low side effect. In 1977, Rotundine was recorded in the Chinese Pharmacopoeia. In 1979, THP achieved a full synthesis, and currently Rotundine is mainly produced by artificial synthesis. From 1980, the study on the mechanisms of Rotundine made great progress. The analgesic effect of Rotundine has nothing to do with opioid receptors or prostaglandins. Rotundine does not belong to narcotic analgesics and antipyretic analgesics. Further, Rotundine has been found to have no affinity with M-cholinergic receptor and GABA system in the brain. But it has affinity to dopamine receptors. The exact mechanisms and pharmacology effects of Rotundine still need more research.