Recent advances in pharmacological intervention for prediabetes / 药学学报

Prediabetes is an abnormal condition between normal glucose metabolism and diabetes mellitus. Impaired glucose tolerance (IGT) is an indicator of high-risk state of prediabetes. Positive interventions of IGT, including life style changes and pharmacological intervention, can effectively postpone and reduce the development of prediabetes into type 2 diabetes mellitus, suggesting that IGT is a key point of diabetes prevention. Currently, pharmacological intervention for prediabetes is still at early stage. In this review, we summarizes recent clinical and preclinical studies on pharmacological intervention for prediabetes, and studies in the development of animal models with IGT and the application of new techniques. We also discuss the prospects of drugs for diabetes prevention, especially with the traditional Chinese medicine.

Recent progress in vaccines against nicotine addiction / 药学学报

Tobacco smoking is a global healthcare problem that poses a substantial and costly health burden. Nicotine is the major constituent responsible for the addiction to tobacco. Current strategies helping tobacco smokers have limited utility in increasing rates of smoking cessation, consequently indicating the need for alternative therapies. A novel therapeutic method is vaccination against nicotine. Nicotine vaccine can generate specific antibodies that can sequester nicotine from cigarette smoke in the blood, and prevent its access to the brain and minimize positive reinforcing effects, which may help smokers to stop smoking. The vaccine will have great potential for the treatment of nicotine addiction and for relapse prevention. Here we will review the current status of vaccines against nicotine addiction and discuss the problems associated with the development of nicotine vaccines.

Effects of (-), (+)-7-hydroxy-clausenamide on synaptic transmission in rat dentate gyrus in vivo / 药学学报

<p><b>AIM</b>To investigate effects of (-), (+)-7-hydroxy-clausenamide (7-OH-Clau) on basal synaptic transmission in the dentate gyrus of anesthetized rats.</p><p><b>METHODS</b>Extracellular recording of the population spike (PS) of hippocampal dentate gyrus following application of low-frequency stimulation (1/30 Hz, 1.0 mA).</p><p><b>RESULTS</b>Fifteen, thirty and sixty minutes after intracerebroventricular (icv) administration of an estimated final brain concentration of 2 x 10(-6) mol.L-1, (-)-7-OH-Clau caused over 30% increase relative to basal PS amplitude before administration, and 27%-41% increase relative to vehicle control (P < 0.05), while (+)-7-OH-Clau exhibited 18%-25% and 11%-20% decrease in the PS amplitude when compared with basal PS amplitude and vehicle control (P < 0.05), respectively.</p><p><b>CONCLUSION</b>The basal synaptic transmission in the dentate gyrus of the rat hippocampus can be potentiated by (-)-7-OH-Clau and attenuated by (+)-7-OH-Clau, indicating that there was a stereoselective difference between the two enantiomers in the modulation of synaptic responses and plasticity.</p>

Enzyme kinetics of clausenamide enantiomers in rat liver microsomes / 药学学报

<p><b>AIM</b>To investigate the enzyme kinetics of (-)3S,4R,5R,6S-clausenamide[(-)-Clau] and (+)-3R,4S,5S,6R-clausenamide[(+)-Clau] catalyzed by rat liver microsomes and compare their stereoselective differences.</p><p><b>METHODS</b>An in vitro metabolic system was built by using rat liver microsomes and NADPH-generating system. Clau and its metabolites were determined simultaneously by a reversed-phase high performance liquid chromatography. The kinetic parameters, K(m), Vmax, and metabolic rate, Vmax/K(m), were calculated by Eadie-Hofstee plot.</p><p><b>RESULTS</b>In the metabolic system, (-)-Clau was found to be mainly metabolized to 7-hydroxy-, 5-hydoxy- and 4-hydroxy-Clau, and 7-hydroxylation was a preferential pathway which exhibited higher Vmax/K(m) value (0.135 microL.min-1.mg-1) than those of 5- and 4-hydroxylation (0.063 and 0.068 microL.min-1.mg-1, respectively). For (+)-Clau, it was mainly metabolized to 4-hydroxy-Clau, whereas 7-hydroxy- and 4-hydroxy-Clau were so small that they could not be detected systematically. 4-Hydroxylation of (+)-Clau showed highest Vmam/K(m) value (0.547 microL.min-1.mg-1) among all the metabolites tested, which was 8.0 times higher than that of 4-hydroxylation of its antipode.</p><p><b>CONCLUSION</b>The data indicated that there were obvious substrate stereoselective differences in the hydroxylation metabolism of (+)- and (-)-Clau, which provided an explanation of the difference of pharmacokinetic characteristics of Clau enantiomers in rats.</p>