Vanilloid receptor agonist capsaicin

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.

Surprisingly, the vanilloid receptor ligand capsaicin supplied the first experimental evidence for the association between SP and nociception (Gasparovic et al., 1964). Capsaicin depletes small primary afferents of at least SP, if not all of their peptide content, and this was accompanied by hypoalgesia. SP depolarizes the ventral root of an isolated rat spinal cord preparation (Konishi and Otsuka, 1974), and has also been shown to excite and/or depolarize neurons in the dorsal root (Urban et al., 1985). Furthermore, in studies on the larger laminae IV and V neurons, the selective agonist, [Sar9,... 

Olvanil [inn, usan] (/V-vanillyloleamide) is a capsaicin analogue regarded as a vanilloid receptor AGONIST. It can be... 

VANILLOID RECEPTOR ANTAGONISTS act at sites activated by sensory irritants, e.g. capsaicin see VANILLOID receptor agonists. Capsazepine, a synthetic compound developed out of vallinoids such as capsaicin, is a high-afflnity competitive vanilloid receptors antagonist. It is used as a pharmacological tool. There is some variation in affinity between different sites and species, suggesting receptor subtypes and species variants. Ruthenium Red also acts as an inhibitor at these sites in a non-competitive manner. 

Fig.3 Chemical structures of two vanilloid receptor agonists olvanil and capsaicin and of the vanilloid...

Daphnanes (C5 (C7 C6) include a variety of cytotoxic, irritant, inflammatory and toxic compounds from the Thymelaeaceae and the Euphorbiaceae. Of particular note are the highly inflammatory PKC activators resiniferatoxin and tinyatoxin from Euphorbia species (Euphorbiaceae) and thymeleatoxin from Thymeka hirsuta (Thymelaeaceae). While the nonester resiniferonol is inactive, the ester (X—CO—O—Y) resiniferatoxin is both an anti-nociceptive vanilloid receptor (capsaicin receptor) agonist and a PKC activator, as is the ester tinyatoxin. 

The mammalian vanilloid subtype 1 capsaicin receptor (VRlr) has been cloned and shown to be activated by plant-derived agonists such as capsaicin (the pungent ingredient in hot chili pepper) and resiniferatoxin (Caterina etal., 1997). Anandamide has been shown to activate the VRlr, resulting in physiological responses that are capsazepine-sensitive and CBR-insensitive (Zygmunt etal., 1999 and Szolcsanyi, 2000). It has also been demonstrated that anandamide acts as full... 

Olvanil (= A-(Vanillyl)-9-oleamide] (vanilloid phenolic) Cholecystokinin receptor Synthetic (cf. Capsaicin) Anandamide transport inhibition [14] (VR agonist) 5.8D... 

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