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.
Research Laboratory, Minophagen Pharmaceutical Co., Ltd., Komatsubara, Zama, Kanagawa 252-0002, Japan.
Yuko
Y
Akasaka
Atsushi
A
Sakai
Kumiko
K
Takasu
Michiko
M
Tsukahara
Akira
A
Hatta
Hidenori
H
Suzuki
Hideo
H
Inoue
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin; D006224:Cricetinae; D004195:Disease Models, Animal; D005557:Formaldehyde; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012584:Sciatic Nerve / Q000601:surgery; D013373:Substance P / Q000494:pharmacology
D000700:Analgesics; D018039:Receptors, Tachykinin; D005557:Formaldehyde; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D006034:Glycyrrhetinic Acid; D002211:Capsaicin; D002118:Calcium