[Development of sigma-receptor ligands and clinical trials].

There are at least two classes of sigma-receptors, termed sigma 1 and sigma 2. Recently, the sigma 1-receptor has been completely sequenced in different species. The amino acid sequences of the different purified proteins are highly homologous, but it shares no homology to know mammalian proteins. These results suggest that the sigma 1 receptor is a distinct entity from any often known receptors. sigma-Receptors are involved in many physiological functions. Therefore, sigma-ligands show many different pharmacological effects such as glucose utilization, neuroprotective, antipsychotic, antidepressive, anxiolytic, nootropic, antiepileptic, antiabuse, antitussive, antidiarrhea, anti-inflammatory, tear protein releasing stimulant and central anti-micturition reflex actions. These results suggest that sigma-receptors are very promising targets for the development of new drugs that have new mechanisms of action.

Effects of traditional Chinese medicines on pharmacokinetics of levofloxacin.

The effects of single coadministrations of one of three traditional Chinese medicines, Hotyu-ekki-to, Rikkunshi-to, and Juzen-taiho-to, on the pharmacokinetics of levofloxacin (LVFX) were investigated with eight healthy volunteers in an open, random crossover fashion. Subjects each received a single oral dose of LVFX (200 mg) alone and then with a single coadministration of each Chinese medicine. There were no significant differences in any pharmacokinetic parameters of LVFX between the groups. Also, no significant changes in the urinary recovery (> 80%) and renal clearance of LVFX were observed. These results indicate that the Chinese medicines tested have no significant effect on the rate and extent of bioavailability or renal excretion of LVFX.

Lack of effect of Chinese medicines on bioavailability of ofloxacin in healthy volunteers.

Recently, Chinese medicines have become available as OTC drugs and are frequently prescribed with Western medicine for the treatment of various chronic diseases. In this study, the effect of the Chinese medicines Sho-saiko-to (TJ-9), Rikkunshi-to (TJ-43) and Sairei-to (TJ-114) on the bioavailability of ofloxacin (OFLX) was investigated in seven volunteers in an open, random crossover fashion. Subjects received a single oral dose of OFLX (200 mg) alone and with coadministrations of each Chinese medicine, at one-week intervals. Plasma and urine samples were analyzed by high-performance liquid chromatography. No significant differences in any estimated bioavailability parameters of OFLX were observed between the two phases. The urinary recovery of OFLX excreted within 24 h after the administration of OFLX alone, 80.6 +/- 3.9% (mean +/- SEM), was not significantly different from those after the coadministrations of the Chinese medicines (79.7 +/- 5.1% for TJ-9, 76.8 +/- 2.3% for TJ-43 and 80.3 +/- 5.3% for TJ-114), suggesting that there was no difference in the systemic availability of the four doses. These findings indicate that the Chinese medicines studied have no significant effect on the rate and extent of bioavailability of OFLX.