ABSTRACT
Eph-ephrin system is emerging as a new potential target in several diseases including cancer, diabetes, neurodegenerative diseases and inflammation. In the last decade, several efforts have been made to develop small molecule antagonists of Eph receptors. Both natural and synthetic compounds were discovered with (poly) phenol and steroidal derivatives on one side and the α1 agonist doxazosin, 2,5-dimethylpyrrol- 1-yl-benzoic acids and amino acid conjugates of lithocholic acid on the other. In the present paper we critically present available data for these compounds and discuss their potential usefulness as pharmacological tools or as candidates for a lead-optimization program.
Subject(s)
Drug Discovery/methods , Ephrins/metabolism , Plant Preparations/pharmacology , Protein Kinase Inhibitors/pharmacology , Receptors, Eph Family/antagonists & inhibitors , Small Molecule Libraries/pharmacology , Animals , Benzoates/chemistry , Benzoates/pharmacology , Cholic Acids/chemistry , Cholic Acids/pharmacology , Doxazosin/chemistry , Doxazosin/pharmacology , Humans , Models, Molecular , Molecular Structure , Plant Preparations/chemistry , Protein Binding , Protein Interaction Mapping , Protein Interaction Maps , Protein Kinase Inhibitors/chemistry , Receptors, Eph Family/agonists , Small Molecule Libraries/chemistryABSTRACT
Doxazosin mesylate (DXM) sustained release pellets were prepared by an extrusion-spheronization and fluid-bed coating technique. The core pellets containing DXM were prepared by extrusion-spheronization technique, and coated by a fluid-bed coater to control the release of DXM. The factors affecting to properties of pellets, such as diluent content, type and coating level of coating agents and plasticizers were studied in the present study. Polymethacrylate derivatives (Eudragit® RS PO and RL PO) were used for coating agents, and polyethylene glycol 6000 (PEG 6000), triethyl citrate (TEC) and castor oil were as plasticizers. To evaluate the properties of prepared pellets, the size of prepared pellets was investigated by sieve analysis technique and the morphology of pellets was evaluated by scanning electron microscopy. Through the dissolution test, factors that have an effect on the dissolution of the drug were evaluated. As the content ratio of microcrystalline cellulose (MCC) had increased, the dissolution was proportionally sustained. Eudragit® RS PO had more marked sustaining effect on the dissolution rate than Eudragit® RL PO, and the effect was more pronounced with the increased coating level. PEG 6000 was an appropriate plasticizer for DXM pellets, and increasing the content of PEG 6000, was also slightly decreasing the dissolution rate.
Subject(s)
Doxazosin/metabolism , Microscopy, Electron, Scanning , Castor Oil/chemistry , Cellulose/chemistry , Citrates/chemistry , Doxazosin/chemistry , Kinetics , Particle Size , Plasticizers/chemistry , Polyethylene Glycols/chemistry , Polymethacrylic Acids/chemistryABSTRACT
PURPOSE: Complementary and alternative medicine, including phytotherapeutic agents, or those derived from plant or herb extracts to treat symptoms, is widely accepted in the community. Men with bothersome lower urinary tract symptoms due to benign prostatic hyperplasia increasingly use such preparations. Phytotherapeutic agent quality is unregulated and in most instances the contents are unknown while erectile dysfunction and prostate cancer treatments have shown contamination with standard pharmaceuticals. Since trial results for benign prostatic hyperplasia phytotherapeutic agents are inconsistent, they may also be contaminated. Thus, we determined whether pharmacological doses of alpha-blockers and/or 5alpha-reductase inhibitors were present in a sample of phytotherapeutic agents for benign prostatic hyperplasia. MATERIALS AND METHODS: We analyzed 15 phytotherapeutic products marketed for benign prostatic hyperplasia. Only oral tablets or capsules were considered with teas, tonics and foods excluded from study. We made random purchases from shop front health stores and Internet retailers. All batches of commercial phytotherapy were analyzed by high performance liquid chromatography. Analysis was semiquantitative using extracts from alfuzosin, doxazosin, terazosin, tamsulosin, dutasteride and finasteride. RESULTS: In the 15 batches of different phytotherapeutic agents tested no interference secondary to contamination with alpha-blockers or 5alpha-reductase inhibitors was observed. CONCLUSIONS: All phytotherapeutic agents for benign prostatic hyperplasia in this study tested negative for alpha-blockers and 5alpha-reductase inhibitors. Inconsistent results in trials using phytotherapeutic agents are probably not explained by the presence of standard pharmaceuticals.