Capsaicin (fig. 2), a naturally occurring vanilloid, is the best known TRPV1 agonist. Resiniferatoxin (RTX) is another naturally occurring vanilloid that exhibits TRPV1 agonistic activity. It is more potent than capsaicin and is currently in development as a sensory neuron desensitizing agent.
Initially, agonists were the major focus of the TRPV1 ligand development due to the analgesic effect resulting from  desensitization of the receptor. However, because of an initial burning effect of all natural vanilloid receptor agonists, including capsaicin, therapy becomes complicated and perhaps ineffective. Attempts to make synthetic agonists with good separation between excitatory effects and the analgesic effects have not been successful. To avoid this persisting side effects of TRPV1 agonists, a focused consideration has been given to competitive antagonists as novel analgesic drugs.