HPLC Determination of tolperisone in human plasma

A simple high performance liquid chromatographic (HPLC) method was developed for the determination of tolperisone in human plasma. Tolperisone and internal standard (chlorphenesin) were isolated from 1 mL of plasma using 8 mL of dichlormethane. The organic phase was collected and evaporated under nitrogen gas. The residue was then reconstituted with 300 mL aliquot of mobile phase and a 100 mL aliquot was injected onto the C18 reverse-phased column. The mobile phase, 45% methanol containing 1% glacial acetic acid and 0.05% 1-hexanesulfonic acid was run at a flow rate of 1 mL/min. The column effluent was monitored using UV detector at 260 nm. The retention times for tolperisone and the internal standard were approximately 7.1 and 8.4 min, respectively. The standard curve was linear with minimal intra-day and inter-day variability. The quantification limit of tolperisone in human plasma was 10 ng/ mL. The proposed method has been applied to the determination of pharmacokinetic profile of tolperisone in Koreans. The Tmax of tolperisone in Koreans (0.94 +/- 0.42 h) was not significantly differ from that reported in Europeans (0.5-1 h), but the mean half-life in Koreans (1.14 +/- 0.27 h) was shorter than that in Europeans (2.56 +/- 0.2 h). The proposed HPLC method is simple, accurate, reproducible and suitable for pharmacokinetic study of tolperisone.     

Effect of imipramine or ECS on central β1 and β2 receptor sensitivity in the cardiovascular response of ratreceptor sensitivity in the cardiovascular response of rat

This study was investigated the effects of imipramine (IMI) and electroconvulsive shock (ECS), which are used as antidepressant therapy, on the central β₁- or β₂ adrenergic receptor in anesthetized rats. The resting blood pressure and heart rate decreased in reserpinized group (5 mg/kg i.p., 24 hr before), but not in other 4 groupsi.e. acute IMI (20 mg/kg i.p. 3–5 hr before), chronic IMI (Same dose, twice a day for 14 days), single ECS (sinusoidal 20 Hz, 120 V for 1 sec) and repeated ECS (same condition, daily for 12 days). The increase of heart rate and hypotension evoked by 1 or 3 μg intracerebroventricular (i.c.v.) administration of (+)dobutamine, β₁-agonist, was attenuated by chronic IMI treatment. The hypotension by salbutamol, β₂-agonist, 1 or 3μg i.c.v. was significantly attenuatted in repeated ECS or reserpine treatment. And, the diminution of pulse pressure of salbutamol also reduced by repeated ECS. These results suggest that IMI or ECS result in attenuation on tachycardia by (+)dobutamine or on hypotension by salbutamol, presumably by which the central β₁ or β₂-receptor sensitivity may be suppressed, respectively.     

Effects of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen in Korean subjects

Archives of Pharmacal Research - The aim of this study was to investigate the impact of CYP2C9*1/*3 genotype on the pharmacokinetics of flurbiprofen and its metabolite. The CYP2C9 genotypes were...     

Signal transduction of bombesin-induced circular smooth muscle cell contraction in cat esophagus

AIM: To investigate the mechanism of bombesin-induced circular smooth muscle cell contraction in cat esophagus. METHODS: Specific G protein or phospholipase C involved in cat esophagus contraction was identified, muscle cells were permeabilized with saponin. After per-meabilization of muscle cells, the Gi3 antibody inhibited bombesin-induced smooth muscle cell contraction. RESULTS: Incubation of permeabilized circular muscle cells with PLC-β3 antibody could inhibit bombesin-induced contraction. H-7, chelerythrine (PKC inhibitor) and genistein (protein tyrosine kinase inhibitor) inhibited bombesin-induced contraction, but DAG kinase inhibitor, R59949, could not inhibit it. To examine which mitogen-activated protein kinase (MAPK) was involved in bombesin-induced contraction, the specific MAPK inhibitors (MEK inhibitor, PD98059 and p38 MAPK inhibitor, SB202190) were used. Preincubation of PD98059 blocked the contraction induced by bombesin in a concentration-dependent manner. However, SB202190 had no effects on contraction. CONCLUSION: Bombesin-induced circular muscle cell contraction in cat esophagus is madiated via a PKC or a PTK-dependent pathway or p44/p42 MAPK pathway.     

Temperature regulates melanin synthesis in melanocytes

Temperature change is one of the major environmental factors that influence the human skin. However, the relationship between temperature and melanogenesis has received little attention. In the present study, we investigated the effects of temperature change on melanogenesis in a mouse melanocyte cell line (Mel-Ab), and primary cultured human melanocytes. We found that Mel-Ab cells cultured at low temperatures (31 and 34 degrees C) produce less melanin than cells at 37 degrees C. These results were confirmed by experiments upon human melanocytes, demonstrating that the hypopigmenting effect of low temperatures is not cell type dependent. The observed melanin production was found to be accompanied by tyrosinase activity at each temperature, indicating that tyrosinase activity is regulated by temperature. We further examined whether the incubation period at low temperatures plays an important role in the regulation of melanogenesis. Short exposures to 27 degrees C for 1 h or 3 h did not affect tyrosinase activity or melanin synthesis, whereas long exposures to 31 degrees C for 2 days or 6 days significantly reduced tyrosinase activity and melanin synthesis in a duration-dependent manner. Our results suggest that exposure to low temperature and the duration of this exposure are important regulators of melanogenesis.