Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper

  title={Resiniferatoxin, a phorbol-related diterpene, acts as an ultrapotent analog of capsaicin, the irritant constituent in red pepper},
  author={Arpad Szallasi and Peter M. Blumberg},

Antifungal and Cytotoxic Activity of Diterpenes and Bisnorsesquiterpenoides from the Latex of Euphorbia resinifera Berg

Investigation of the effects of major compounds of the latex of E. resinifera on the yeast Saccharomyces cerevisiae, on the growth of Aspergillus carbonarius, and on the breast cancer cell line MCF7 as well as on MCF10A normal breast cells found treatment with these compounds led to a specific cytotoxic effect and the increase in the level of intracellular ROS.

The potent irritancy of the daphnane orthoester, resiniferatoxin, exhibits features of a mixed aetiology

It is concluded that the erythema response to resiniferatoxin has a mixed aetiology, which may explain the unique potency of this toxin.

Synthesis and evaluation of phorboid 20-homovanillates: discovery of a class of ligands binding to the vanilloid (capsaicin) receptor with different degrees of cooperativity.

Phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV, 6a), a compound which abolished binding cooperativity, was further tested in a variety of in vivo assay used to characterize vanilloid-like activity.

Dialdehyde sesquiterpenes and other terpenoids as vanilloids.

Resiniferatoxin‐Amide and Analogues as Ligands for Protein Kinase C and Vanilloid Receptors and Determination of Their Biological Activities as Vanilloids

The amide analogue of RTX was also 20‐ and 300‐fold less potent than RTX in inducing chemogenic pain and hypothermia, respectively, indicating that both new compounds induced apparent positive cooperativity among vanilloid binding sites.

[3H]resiniferatoxin binding by the vanilloid receptor: species-related differences, effects of temperature and sulfhydryl reagents

Preincubation with heavy metal cations and other sulfhydryl-reactive agents inhibited specific [3H]RTX binding indicating that the vanilloid receptor is a thiol-protein, and that free sulfHydryl groups play an essential role in agonist binding activity.



Sensory effects of capsaicin congeners I. Relationship between chemical structure and pain-producing potency of pungent agents.

A quantitative method for measuring the efficiency of pungent agents of capsaicin-type by the pain reaction elicited on the eye of rats and a hypothetical pharmacological receptor for Capsaicin on pain sensory nerve endings is presented.

Different biological targets for resiniferatoxin and phorbol 12-myristate 13-acetate.

It is reported that resiniferatoxin is 100- to 1000-fold less active than is phorbol 12-myristate 13-acetate in in vitro assays with both chicken and mouse fibroblasts, and further evidence that the fibroblast target may be homologous to that involved in promotion.

Structure-activity relations of polyfunctional diterpenes of the daphnane type. I. Revised structure for resiniferatoxin and structure-activity relations of resiniferonol and some of its esters.

Reesterification of III with homovanillic acid showed that the previously proposed structure for resiniferatoxin has to be revised to resiniferonol-9, 13, 14-orthophenylacetate-20-(4-hydroxy-3-methoxyphenyl) acetate, and some aspects of structure-activity relations of irritancy of resinifer onol esters are established and discussed.

Phorbol ester induction of 8-lipoxygenase in inbred SENCAR (SSIN) but not C57BL/6J mice correlated with hyperplasia, edema, and oxidant generation but not ornithine decarboxylase induction.

Several responses suggested to be critical components of phorbol ester tumor promotion were compared in 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion-sensitive SSIN and TPA promotion-resistant C57BL/6J mice, and oxidant generation or possibly 8-lipoxygenase activity may be the basis for the sensitivity or resistance to TPA as a hyperplasiogen and as a tumor promoter.

Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin.

The question of the role played by the sensory nerves in the mechanism of the inflammatory response arose at the beginning of this century and was almost entirely neglected in modem research and experimental work has been confined mainly to the study of axon reflex flare in human skin.

Specific binding of phorbol ester tumor promoters.

The data suggest that biological responses to thephorbol esters in chicken embryo fibroblasts are mediated by this binding activity and that the binding activity corresponds to the phorbol Ester target in mouse skin involved in tumor promotion.

Tumor initiators and promoters in the induction of Epstein-Barr virus.

A series of compounds, representing three classes of tumor-promoting diterpene esters, efficiently induced EBV in persistently infected cells, and prostaglandins, reported to be released after treatment with tumor promoters, were ineffective in virus induction under the conditions tested.