Suppressive effects of glycyrrhetinic acid derivatives on tachykinin receptor activation and hyperalgesia

Glycyrrhetinic acid (ga),an aglycone of glycyrrhizin,isolated from the licorice root (glycyrrhizia),and its semi-synthetic derivatives have a wide range of pharmacological effects. to investigate whether ga derivatives may be used as a new class of analgesics,we examined the effects of these compounds on human tachykinin receptors expressed in cho-k1 cells. among the ga derivatives examined,the disodium salt of olean-11,13(18)-dien-3β,30-o-dihemiphthalate inhibited the mobilization of [ca 2+] i induced by substance p,neurokinin a,and neurokinin b in cho-k1 cells expressing the human nk 1,nk 2,and nk 3 tachykinin receptors,respectively. in an inflammatory pain model,compound 5 suppressed the capsaicin-induced flinching behavior in a dose-dependent manner. compound 5 was also effective in suppressing pain-related behaviors in the late phase of the formalin test and reducing thermal hyperalgesia in the neuropathic pain state caused by sciatic nerve injury. collectively,compound 5 may be an analgesic candidate via tachykinin receptor antagonism. © the japanese pharmacological society.