Resiniferatoxin from Euphorbia resinifera

Resiniferatoxin (RTX) is the toxin isolated from the spurge Euphorbia resinifera which is responsible for the powerful burning sensation and skin irritation induced by the milky sap of these plants. Like capsaicin, resiniferatoxin activates TRPV1 currents, but not the currents through other members ofthe TRPV subfamily. 

In 1990, specific binding of [ H]resiniferatoxin (2, RTX), an ultrapotent capsaicin analogue isolated from the latex of the cactus-like plant Euphorbia resinifera, provided the first direct proof for the existence of a distinct capsaicin receptor [4]. Based on the chemical motif (a vanillyl moiety) shared by (1) and (2), this receptor was termed the vanilloid receptor VRl [1]. 

Scheme 1 Chemical structures of natural vanilloid receptor agonists a, capsaicin, the irritant principle in hot peppers b, resiniferatoxin (RTX), isolated from the cactuslike plant Euphorbia resinifera c, the triprenyl phenol scutigeral, found in an edible, non-pungent mushroom d, the sesquiterpenoid dialdehyde isovelleral, found in pungent mushrooms.

Resiniferatoxin (RTX) is a daphnane diterpenoid contained in the irritant latex of some succulent African Euphorbias. Its total synthesis has been described as a 40 step asymmetric synthesis (Wender et al., 1997 see below), but for clinical use RTX isolated from Euphorbia resinifera. 

The best-known vanilloids are capsaicin and resiniferatoxin (RTX). Capsaicin is the compound in various types of hot peppers that gives them their characteristic hot and spicy flavor. It is used in a variety of products ranging from personal-defense pepper sprays to squirrel-proof birdseed. RTX is a powerful irritant extracted from a cactuslike plant. Euphorbia resinifera. The milky latex obtained from the plant is referred to in medical literature dating as far back as the first century. In these writings, it was described as a nose and skin irritant and as a treatment for chronic pain. In powdered form, RTX causes sneezing, a characteristic used by some practical jokers. 

Daphnanes are more frequently found such as daphnetoxin in flowers and bark of Daphne species exemplified by Daphne mezereum (Thymeliaceae), irritating human skin and mucous membranes, as well as (+)-resiniferatoxin from Euphorbia resinifera and related species. Some daphnanes are reported to have antineoplastic and antileukemic activities. 

The vanilloid receptor is also known to be strongly affected by a capsaicin analog compoimd called resiniferatoxin, which was first isolated from a cactus-like plant Euphorbia resinifera). Lafutidine, an antacid, is more efficient against ulcers than other similar medicines, which may also be the consequence of an interaction with the vanilloid receptor. 

Resiniferatoxin, RTX, (19) is also an important drug isolated from the latex of Euphorbia resinifera, known since ancient times with the name euphorbium and used as purgatives, to remove warts and as a cathartic, in asthma and bronchial catarrh [30]. RTX is an ultrapotent vanilloid in clinical trials for bladder hyperiflexia and diabetic neuropathy [31]. 

Capsaicin (42), a pungent principle in chili peppers Capsicum spp.), as well as the skin irritant, resiniferatoxin (43), from the latex of Euphorbia resinifera, have been used to probe the transient receptor potential (TRP) channels and the vanilloid receptors responsible for the pain sensation caused by heat. This has led to the successful isolation of the first nociceptive receptor, TRPVI (transient receptor potential channel, vanilloid subfamily member 1) [103, 104], Capsaicin-containing creams are now available as nonprescription pain-relievers for the treatment of post-therapeutic neuralgia [105]. The internal use of capsaicin for the treatment of severe post-operative pain, post-traumatic neuropathic pain, and musculoskeletal diseases is currently under clinical trial [106]. 

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