Biol. Pharm. Bull. 28(5) 845—848 (2005)

been detected in central nervous system of rodents, nonhuman primates and human based on radioligand binding studies. KOR agonists may have pharmacotherapeutic potential in the treatment of pain or hyperalgesia and in the management of psychostimulant addiction. However, the clinical application of selective KOR agonists, such as ethylketocyclazocine and U-50488, has been limited by the occurrence of characteristic undesirable effects, e.g. aversion, sedation and dysphoria. ( )-Matrine (matridin-15-one) and its C-6 epimer, ( )-allomatrine, are the typical lupine alkaloid along with lupinine, sparteine and cytisine (Fig. 1). These alkaloids occur in many leguminous plants, especially in the genus Sophora and are one of the main basic constituents in both Sophora flavescens and S. tonkinensis. Dry roots of these plants have been used as important Chinese drugs ‘Ku-shen’ and ‘Shan-dougen’ respectively, for the treatment of fever and as analgesics. We previously demonstrated that ( )-matrine, when given s.c., induced a dose-dependent antinociceptive effect, which was identical to that of pentazocine, in the acetic acid-induced abdominal contraction test. ( )-Allomatrine also showed its antinociceptive property with one-third the potency of that of ( )-matrine. It should be noted that either ( )-matrineor ( )-allomatrine-induced antinociceptive effect was markedly inhibited by s.c.-pretreatment with a selective KOR antagonist nor-binaltorphimine (nor-BNI), indicating the critical role of KOR in antinociceptive effects of these alkaloids. These findings pointed out the possibility that either ( )-matrine or ( )-allomatrine, which possess the distinct chemical structure from conventional KOR agonists, may be candidate for the effective option for the pain control in the clinical. It is, therefore, worthwhile to further ascertain the antinociceptive properties of ( )-matrine and ( )-allomatrine. Thus, the goal of the present study was to investigate the possible involvement of either supraspinal or spinal KORs in antinociceptive effects induced by ( )-matrine or ( )-allomatrine.