This paper describes the discovery of a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1), as a potent antioxidant agent against lipid peroxidation. The structure-activity relationship of edaravone indicated that lipophilic substituents were essential to show its lipid peroxidation-inhibitory activity. In vivo studies revealed that edaravone showed brain-protective activity in a transient ischemia model.

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We have used Heidenhain-pouch dogs to investigate the effects of (+/-)-5-methoxy-2-{[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulph inyl}-1H-imidazo[4,5-b]pyridine (TU-199), an imidazopyridine derivative, on gastric acid secretion stimulated by histamine, carbachol and tetragastrin. We have also investigated the duration of the antisecretory effect of TU-199 using a measurement of intragastric pH for 24 h in gastric fistula dogs whose gastric acid secretion was stimulated by histamine. Single oral administration of TU-199 (0.1, 0.2 and 0.4mgkg(-1)) dose-dependently suppressed gastric acid secretion stimulated by histamine infusion. Oral treatment with TU-199 (0.2, 0.4 and 0.8 mg kg(-1)) also dose-dependently inhibited acid secretion induced by carbachol and tetragastrin. The inhibitory effect of TU-199 on stimulated gastric acid secretion was more potent than that of omeprazole, a well-known H+,K(+)-ATPase inhibitor in dogs. Repeated oral treatment with TU-199 at a dose of 0.2 mg kg(-1) once a day for seven days markedly suppressed histamine-stimulated gastric acid secretion in dogs. This inhibitory effect of TU-199 reached a maximum level after three or four doses and was more pronounced than that of omeprazole or lansoprazole. In gastric fistula dogs, the duration of intragastric pH-elevation by administration of TU-199 (0.3 mg kg(-1)) was much longer than that of omeprazole (0.6mgkg(-1)) or lansoprazole (0.9mgkg(-1)). The IC50 values (doses resulting in 50% inhibition) of TU-199, omeprazole and lansoprazole with regard to H+,K(+)-ATPase activity in dog gastric mucosal microsomes were 8.6, 8.8 and 9.9 microM, respectively. These results indicate that TU-199 inhibits gastric acid secretion via suppression of a H+,K(+)-ATPase activity. Our findings also suggest that TU-199 might have potent and long-lasting effects on gastric acid secretion.

Preterm labor (PTL) is one of the main causes of fetal mortality and morbidity in obstetrical medicine. Current methods of treatment are not very effective and often have significant side effects. For this reason new methods of preventing PTL are currently being sought. In Western medicine the newest development is oxytocin antagonists. In Oriental medicine acupuncture and moxibustion are being utilized for the purpose of stopping PTL. The goals of this study were to determine if acupuncture in pregnant rats can suppress oxytocin induced uterine contractions and to compare these results with those inhibited by an oxytocin antagonist. Uterine contractions were induced by continuous infusion of exogenous oxytocin. The first fetus in one uterine horn near the ovarian end was removed and distilled water-filled catheter was inserted into that vacated amniotic sac to measure uterine contractions as intrauterine pressure changes. Two acupoints of Ho-Ku (LI-4) and San-Yin-Chiao (Sp-6) were selected for acupuncture and Kuan-Yüan (Co-4) was used for moxibustion. The oxytocin-induced uterine contractions were significantly suppressed by acupuncture on the LI-4 (p < 0.05), but not by Sp-6. Stimulation of Co-4 by moxibustion had no significant (p > 0.05) tocolytic effect. The administration of oxytocin antagonist eliminated all the uterine contractions induced by oxytocin. The application of acupuncture to re-stimulate the activity that was suppressed by the oxytocin antagonist did not produce any positive results. However, prostaglandins did cause the uterus to contract. In conclusion, acupuncture on LI-4 was found to suppress uterine contractions induced by oxytocin in the pregnant rat. If acupuncture is similarly effective in counteracting the effects of oxytocin in women, then this may an alternative medical treatment for women in preterm labor.