text: Capsaicin (fig. 2) has three functional regions: an aromatic A region where a parent homovanillyl (3-methoxy 4-hydroxybenzyl) group is optimal, a B region known as the ester or amide linker and the aliphatic C region where a lipophilic octanyl moiety is associated with the highest potency. The homovanillyl motif and amide bond regions contain dipolar groups which are implicated in hydrogen bonding interactions.
  Phenolic hydroxide and amide moieties appear to be vital for inducing capsaicin responses. Removal of the phenolic hydroxide or amide bond in capsaicin analogues leads to reduction of potency. The phenolic hydroxide and amide moieties in capsaicin share potential multiple hydrogen bond interactions with the TRPV1 receptor. Capsaicinoids and capsinoids are characterized by an oxygenated aromatic moiety bound via an amide (capsaicinoids) or ester (capsinoids) linker to a lipophilic acyl group. The vanillyl and carbonyl linker contain polar groups capable of forming hydrogen bonds essential for activity, whereas the lipophilic moiety interacts with a corresponding cleft of the vanilloid binding site on TRPV1. Replacement of the medium-sized branched fatty acid of capsaicin with longer fatty acids is damaging for activity, but the presence of unsaturations restores and potentiates activity e.g. oleoylvanillamine (olvanil)(fig. 3a), is 10-fold more potent than capsaicin in TRPV1 activation assays.