Biphasic effects of Morus alba leaves green tea extract on mice in chronic forced swimming model.

In this study, the effects of an aqueous extract of Morus alba leaves green tea (ME) on mouse behaviors (depression, anxiety, climbing activity and thermal response), muscle coordination and muscle strength were studied. Male IRC mice received a single intraperitoneal injection of either the ME, desipramine or diazepam. Thirty minutes after injection, the mice were tested in all experimental models. A significant antidepressant-like effect could be detected in the animals receiving either 100 or 200 mg/kg ME. The effect of 200 mg/kg ME in decreasing the immobility time was comparable to 10 mg/kg desipramine. With higher dose (1000 mg/kg), a significant increase in immobility time could be observed. In the elevated plus maze, no increase in time in the open arm could be observed in mice treated with ME at either 100 or 200 mg/kg. However, high doses of ME (500 or 1000 mg/kg) decreased both time in the open arm and the number of entries in the maze. No change in thermal response could be seen in mice treated with ME at doses up to 500 mg/kg, however, at 1000 mg/kg, the response time to heat was increased significantly. The ME at either 500 or 1000 mg/kg also decreased muscle coordination, strength and climbing activity significantly when compared with the control. This study suggests that ME possesses an antidepressant- without an anxiolytic-like effect, however, at high doses, the extract might show the sedative effect and alter other functions such as muscle strength, animal activity in the maze and pain response.

Psoralen analogues: synthesis, inhibitory activity of growth of human tumor cell lines and computational studies.

Eight psoralens have been evaluated for their ability to inhibit the in vitro growth of three human tumor cell lines representing different tumor types, MCF-7 (breast cancer), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer). The synthesis of four new psoralens (benzofurocoumarins) is presented as well as the results of the ab initio calculations to find the parameters that relate the structure with the antitumor activity. This work provides supplementary information that could allow the development of new psoralen analogues with this type of biological activity.

Steady-state bioequivalence study of clozapine tablet in schizophrenic patients.

PURPOSE: To compare the bioavailability of two clozapine formulations (100 mg Clozaril tablet from Novartis Pharmaceuticals UK Ltd., UK, as a Reference formulation and 100 mg Cloril tablet from Atlantic Laboratories Corp., Ltd., Thailand, as a Test formulation). The present study was conducted under real-life conditions in schizophrenic patients using a steady-state, multiple-dose, randomized crossover design to avoid the risk of adverse effects in healthy volunteers and pharmacokinetic difference between single and multiple-dose of the drug. METHODS: The subjects received 100 mg bid of either the Reference formulation or the Test formulation for 7 days. At day-7 of each study phase, blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h after drug administration. Plasma was separated and stored at -80 degrees C until assay. The plasma concentration of clozapine was determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated from the observed plasma-concentration time profiles. The bioequivalence between the two formulations was assessed by calculating individual peak plasma concentrations (Cmax) and area under the concentration-time curve (AUC(0-12 h)) ratios. RESULTS: All subjects well tolerated both clozapine formulations. No serious side effects were reported. The Tmax, terminal half-life and the total plasma clearance of clozapine (uncorrected for bioavailability) observed in the present study were comparable to those observed in other previous reports. All of the pharmacokinetic parameters investigated in the present study calculated from the subjects after administration of Test and Reference formulations were close. The 90% confident interval for the ratio of means for the lnCmax (0.9784-1.0622) and lnAUC(0-12h) (0.9559-1.0441) are within the guideline range of bioequivalence (0.80 to 1.25). CONCLUSION: The result demonstrated that the Test formulation was bioequivalent to the Reference formulation (Clozaril) when orally administered in schizophrenic patients, in terms of both the rate and extent of absorption.

Cytotoxic activity of lupane-type triterpenes from Glochidion sphaerogynum and Glochidion eriocarpum two of which induce apoptosis.

Six known lupanes lupenone ( 1), 3- epi-lupeol ( 2), glochidone ( 4), glochidonol ( 5), glochidiol ( 6) and lup-20(29)-ene-1beta,3beta-diol ( 7) were isolated from the roots and stem wood of Glochidion eriocarpum and three, 5, 6 and lup-20(29)ene-3alpha,23-diol ( 3), were isolated from the roots and stem wood of Glochidion sphaerogynum. Compounds were identified by (1)H- and (13)C-NMR techniques. Triterpenes 2 - 7 were tested against the growth of three human tumor cell lines, MCF-7, NCI-H-460 and SF-268. Lupanes 3, 5, and 6 exhibited strong inhibitory effects against all three; thus GI (50) values for 3 were 12.7 +/- 3.7, 17.9 +/- 1.1 and 17.9 +/- 0.5, for 5 9.0 +/- 3.7, 4.9 +/- 0.2 and 9.8 +/- 0.5, and for 6 6.63 +/- 0.7, 7.5 +/- 0.5 and 9.7 +/- 0.3.3. Epilupeol was less active, with GI (50) values of 75.6 +/- 11.7, 86.1 +/- 12.4 and 80.9 +/- 2.6 while 7 was moderately active only against MCF-7 (GI (50) = 79.2 +/- 2.4). Additional studies indicated that triterpenes 5 and 6 exerted their antiproliferative activity through the involvement of apoptosis while triterpene 3 did not.

Synthesis and evaluation of N1-substituted-3-propyl-1,4-benzodiazepine-2-ones as cholecystokinin (CCK2) receptor ligands.

A novel synthetic approach towards N1-alkylated 3-propyl-1,4-benzodiazepines was developed in five synthetic steps from 2-amino-4-chlorobenzophenone, in which the N-oxide 4 served as a key intermediate. The structure-activity relationship optimization of this 3-propyl-1,4-benzodiazepine template was carried out on the N1-position by selective alkylation reactions and resulted in a ligand with an improved affinity on the cholecystokinin (CCK2) receptor. The N-allyl-3-propyl-benzodiazepine 6d displayed an affinity towards the CCK2 (CCK-B) receptor of 170 nM in a radiolabelled receptor-binding assay. The anxiolytic activity of this allyl-3-propyl-1,4-benzodiazepine 6d was subsequently determined in in-vivo psychotropic assays. This novel ligand had ED50 values of 4.7 and 5.2 mg kg(-1) in the black and white box test and the x-maze, respectively, and no significant sedation/muscle relaxation was observed.