Pharmacology of sinomenine, an anti-rheumatic alkaloid from Sinomenium acutum

The root and stem decoctions of Sinomenium acutum Rehd. et Wils. (formerly Sinomenium diversifolius Diels, one type of Fang-chi (Chinese)) have been used as a folk remedy for neuralgia and rheumatoid arthritis in many areas of the Far East. In Japan and China various viny plants have been identified as Fang-chi (Boi in Japanese) since antiquity. This uncertain nomenclature has made it difficult to evaluate the efficacy of the Fang-chi described in the classic literature. Among traditional Fang-chi plants only Sinomeniumacutum has been demonstrated to contain the alkaloid sinomenine, which is now known to be effective in neuralgia and rheumatic diseases. Sinomenine is a unique plant alkaloid, as it potently releases histamine in association with degranulation of tissue mast cells in mammalian tissues. This action occurs preferentially in the skin and joint capsules. The released histamine is responsible for the dominant pharmacological actions of sinomenine, such as vasodilatation, increased vascular permeability, acceleration of the thoracic and peripheral lymph flow, contraction of plain muscles, increased peristalsis of the intestines, and stimulation of gastric acid secretion. At toxic doses of sinomenine, convulsive central excitation was observed in most laboratory animals. Clinical side effects encountered with high doses of injected sinomenine or of decocted Sinomenium acutum were: injection site flare, pruritus in the head and upper part of the body, edema around the lips and eyelids, and temporary cephalalgia. Most of these side effects were reduced by classical antihistamines (H1-receptor antagonists). Daily subcutaneous injections of sinomenine for more than one week produced an analgesic effect in mice. Granulation tissue growth and adjuvant arthritis induced in rats were both inhibited by daily injections of a small dose of sinomenine hydrochloride or histamine dihydrochloride. These inhibitory effects were mediated through histamine H2-receptors probably on fibroblasts (for granulation tissue growth) and on T-cells (for adjuvant arthritis), since these effects were clearly inhibited by the H2-antagonist burimamide but not by the H1-antagonist mepyramine. The anti-rheumatic effect on Sinomenium acutum are probably genuine and can probably be attributed to the histamine-releasing properties of sinomenine.