Occurrence of the Synthetic Analgesic Tramadol in an African Medicinal Plant

摘要

Initiating a research program aimed at discovering natural products as pain relievers, we focused our attention on the sub-Saharan Nauclea latifolia Sm. (Rubiaceae) plant, commonly known as African peach or pincushion tree. This plant has a long tradition of use by local populations for the treatment of a wide diversity of illnesses, including severe digestive problems, neurological disorders and infectious diseases. In Cameroon, the plant is used to treat pain, malaria, fever, epilepsy, and infantile convulsions. We were particularly interested in the traditional use of the root bark of N. latifolia in pain relief. Previous phytochemical investigation of N. latifolia led to the identification of alkaloids, mostly naucleamides, as the main constituents Extracts from this plant have shown antipyretic, antinociceptive/ anti-inflammatoryand antimalarial activities. In this study, a fractionation of the crude extract, guided by the antinociceptive bioactivity, led to the isolation of a potent analgesic compound, which was identified as (±)-cis-2-[(dimethylami-no)methyl]-1-(3-methoxyphenyl)cyclohexanol, commonly known by its international non-proprietary name (INN), tramadol. Tramadol was first manufactured by Grilnenthal GmbH (Germany) and was brought into clinical usage in the late 1970s.