Pharmacokinetics and pharmacodynamics of a novel Acetylcholinesterase Inhibitor, DMNG-3.

DMNG-3(3ß-Methyl-[2-(4-nitrophenoxy)ethyl]-amino]con-5-enine), is a new and the potentially most potent acetylcholinesterase inhibitor recently obtained from conessine by N-demethylation and nucleophilic substitution reaction. In the present study, a step-down passive avoidance test was used to investigate whether DMNG-3 could modulate impairment of learning and memory induced by scopolamine, and a high performance liquid chromatography(HPLC) method for the determination of DMNG-3 in biological samples was applied to study its pharmacokinetics and tissues distribution. Separation was achieved on C18 column using a mobile phase consisting methanol-water (70:30, v/v) at a flow rate of 1.0ml/min. The intra- and inter-day precisions were good and the RSD was all lower than 1.30%. The mean absolute recovery of DMNG-3 in plasma ranged from 88.55 to 96.45 %. Our results showed oral administration of DMNG-3(10,25,50 mg/kg/day) can significantly improve the latency and number of errors and had a positive effect of improvement of learning and memory in mice in passive avoidance tests. The elimination half-life (T1/2) was 14.07±1.29, 15.87±1.03h, and the total clearance (CL) values were 0.70±0.11, 0.78±0.13 L/h/kg, respectively. The pharmacokinetic studies showed that DMNG-3 has a slowly clearance and large distribution volume in experimental animals, and its disposition is linear over the range of doses tested. The liver, small intestine, stomach, and large intestine were the major distribution tissues of DMNG-3 in mice. It was found that DMNG-3 could be detected in brain, suggesting that DMNG-3 can cross the blood-brain barrier. The present study shows that DMNG-3 can be possible developed as a new drug for the treatment of Alzheimer's disease in the future.

Isolation and structure identification of chemical constituents from Anabasis brevifolia / 药学学报

<p><b>AIM</b>To study the chemical consitituents of the n-butanol-extracts of Anabasis salsa and Various chromatographic techniques were used to the chloroform-extract of Anabasis brevifolia.</p><p><b>METHODS</b>separate and purify the constituents. Their physico-chemical properties and spectral data were used to elucidate their structures.</p><p><b>RESULTS</b>Five compounds were isolated and identified as 2-O-beta-D-glucopyranosyloxy-4,6-dimethoxy phenylenthanone (1), 2-O-(2)-beta-D-glucopyranosyloxy-4, 6-dimethoxy phenylenthanone (2), 3-methyl-but-2-enoic acid-[2-(4-methoxy phenyl)-ethyl]-amide (3), 5,6,7,2'-tetramethoxy isoflavonoid (4), 2'-hydroxy-5,6,7-trimethoxyisoflavonoid (5).</p><p><b>CONCLUSION</b>Compounds 2, 3, and 5 are new compounds. And the others were isolated from Anabasis L. for the first time.</p>

Isolation and identification of two new epimer from the mother liquid of megestrol acetate / 药学学报

<p><b>AIM</b>To study the impurity in the drug megestrol acetate.</p><p><b>METHODS</b>Chromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis.</p><p><b>RESULTS</b>Two new epimers were isolated from the mother liquid of the drug megestrol acetate.</p><p><b>CONCLUSION</b>These new epimers were identified as 17alpha-acetoxy-2beta,6alpha-dimethylprega-4-ene-3,20-dione (1) and 17alpha-acetoxy-2alpha,6alpha-dimethylprega-4-ene-3,20-dione (2).</p>

The isolation and identification of two new epimer from the mother liquid of testosterone / 药学学报

<p><b>AIM</b>To study the impurity of the drug testosterone.</p><p><b>METHODS</b>Chromatography methods were used to separate the chemical constituents. Their structures were determined by NMR and MS spectral analysis.</p><p><b>RESULTS</b>Two new epimers were isolated from the mother liquid of the drug.</p><p><b>CONCLUSION</b>These new epimers were identified as 3alpha-ethoxyandrost-4-en-17beta-ol, 3beta-ethoxyandrost-4-en-17beta-ol.</p>