Possible role for anisodamine in organophosphate poisoning

Abstract

In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison‐directed antidotes, patients may require extra oxygen and artificial ventilation; other modalities may also be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs from this family is non subtype‐selective muscarinic, and a nicotinic cholinoceptor antagonist, which has been employed in traditional Chinese medicine. As a muscarinic antagonist, it displays similar pharmacological effects to atropine and scopolamine. However, anisodamine is not only less potent than atropine and scopolamine but also less toxic. Current in vitro and animal model studies have demonstrated that anisodamine has protective effects in a variety of diseases. Organophosphate poisoning involves not only the central and peripheral nervous systems, but also the cardiac and respiratory systems, as well as activation of inflammatory processes and oxidative stress. Therefore, the anticholinergic and additional activities of anisodamine appear to be relevant and justify its consideration as an addition to the existing remedies. However, more research is needed, as at present data on the role of anisodamine in the management of organophosphate poisoning are limited. Here, we review the beneficial effects of anisodamine on processes relevant to organophosphate poisoning.

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“…Anisodamine is a belladonna alkaloid, which is isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza belonging to the Solanaceae family [50,51]. It is mainly used to relieve circulatory diseases in clinical conditions such as disseminated intravascular coagulation (DIC) and skeptic shock [52,53]. The research of Yu et al [54] showed that anisodamine activated a 7 nicotinic acetylcholine receptor (a7nAChR) to increase the level of serum estradiol.…”

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“…[7]. It has been used for many diseases, such as respiratory diseases, various circulatory disorders, septic shock, gastric ulcers, migraine, gastrointestinal colic, acute glomerular nephritis, eclampsia, rheumatoid arthritis, obstructive jaundice, opiate addiction, organophosphorus poisoning, and snake bite, as well as in radiation damage protection, due to its ability to improve microcirculation [8,9]. Anisodamine had also been used to treat patients of severe acute respiratory syndrome (SARS) with hypoxemia in 2003 [10].…”

Isolation, expression and biochemical characterization of recombinant hyoscyamine-6β-hydroxylase from Brugmansia sanguinea – tuning the scopolamine production

“…Recently it has been shown that 6β-hydroxyhyoscyamine (2) (anisodamine), the biosynthetic intermediate between hyoscyamine (1) and scopolamine (3), has the lowest neurotoxicity, suggesting this drug as new therapeutic agent against Alzheimer's disease and organophosphate poisoning. 3 Despite their beneficial pharmaceutical properties and high therapeutic demand, the lack of high yielding and stereospecific total synthesis approaches, requires the production of 1-3 to rely on plant ex-traction. 1,4 Therefore the exploration of new reliable plant sources is of crucial interest.…”