“For export only” medicines come back to Europe: A RP-LC method for the screening of six glucocorticoids in illegal and counterfeit anti-inflammatory and lightening creams

“For export only” anti-inflammatory and lightening creams are medicinal products sold in African countries for their skin whitening action. In the last years, Rapid Alerts from European Medicinal Regulatory Agencies evidenced the presence of a large number of illegal and counterfeit anti-inflammatory products advertised for their whitening action on black skin in the European market.     

Interactions of human serum albumin with meloxicam: Characterization of binding site

Human serum albumin (HSA) is the most prominent protein in plasma. The three-domain design of HSA provides a variety of binding sites for many ligands, including heme, bilirubin and drugs. Here, we report the effect of new generation, non-steroidal anti-inflammatory drug (NSAID) meloxicam on the albumin conformation and ligand binding. In the present work the interaction of meloxicam with HSA in aqueous solution at physiological pH has been investigated through circular dichroism and fluorescence spectroscopy. The strong quenching of the fluorescence clearly indicated that the binding of the drug to HSA changed the microenvironment of tryptophan residue and the tertiary structure of HSA. This was confirmed by the destabilization of the warfarin binding site. CD and fluorescence spectroscopic results showed marked reductions (about 40% decrease in the CD Cotton effect intensity, and ∼15% decrease of the fluorescence intensity) in the affinity of albumin for bilirubin upon meloxicam binding. The strong inhibition of warfarin and ANS bound to protein after meloxicam modification compared with aspirin confirms that the binding site of both drugs is not the same.     

The SUMMIT Trial:: A field comparison of buprenorphine versus methadone maintenance treatment

This prospective patient-preference study examined the effectiveness in practice of methadone versus buprenorphine maintenance treatment and the beliefs of subjects regarding these drugs. A total of 361 opiate-dependent individuals (89% of those eligible, presenting for treatment over 2 years at a drug service in England) received rapid titration then flexible dosing with methadone or buprenorphine; 227 patients chose methadone (63%) and 134 buprenorphine (37%). Participants choosing methadone had more severe substance abuse and psychiatric and physical problems but were more likely to remain in treatment. Survival analysis indicated those prescribed methadone were over twice as likely to be retained (hazard ratio for retention was 2.08 and 95% confidence interval [CI] = 1.49–2.94 for methadone vs. buprenorphine), However, those retained on buprenorphine were more likely to suppress illicit opiate use (odds ratio = 2.136, 95% CI = 1.509–3.027, p < .001) and achieve detoxification. Buprenorphine may also recruit more individuals to treatment because 28% of those choosing buprenorphine (10% of the total sample) stated they would not have accessed treatment with methadone.     

Allosteric modulators of the hERG K channel: Radioligand binding assays reveal allosteric characteristics of dofetilide analogs

Drugs that block the cardiac K⁺ channel encoded by the human ether-à-go-go gene (hERG) have been associated with QT interval prolongation leading to proarrhythmia, and in some cases, sudden cardiac death. Because of special structural features of the hERG K⁺ channel, it has become a promiscuous target that interacts with pharmaceuticals of widely varying chemical structures and a reason for concern in the pharmaceutical industry. The structural diversity suggests that multiple binding sites are available on the channel with possible allosteric interactions between them. In the present study, three reference compounds and nine compounds of a previously disclosed series were evaluated for their allosteric effects on the binding of [³H]astemizole and [³H]dofetilide to the hERG K⁺ channel. LUF6200 was identified as an allosteric inhibitor in dissociation assays with both radioligands, yielding similar EC₅₀ values in the low micromolar range. However, potassium ions increased the binding of the two radioligands in a concentration-dependent manner, and their EC₅₀ values were not significantly different, indicating that potassium ions behaved as allosteric enhancers. Furthermore, addition of potassium ions resulted in a concentration-dependent leftward shift of the LUF6200 response curve, suggesting positive cooperativity and distinct allosteric sites for them. In conclusion, our investigations provide evidence for allosteric modulation of the hERG K⁺ channel, which is discussed in the light of findings on other ion channels.     

Testing strategies for embryo-fetal toxicity of human pharmaceuticals. Animal models vs. in vitro approaches : A workshop report

Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives.     

Relationship between anxiety disorders and opiate dependence— A systematic review of the literature : Implications for diagnosis and treatment

Our objective was to evaluate the prevalence and temporal sequence of co-occurrence of anxiety disorders with opiate dependence in order to better define the relationship between these two disorders and to improve diagnosis and treatment. The search used Medline and Toxibase up to January 1, 2009, and was based on a systematic review method. Eighteen studies were found. Prevalence of anxiety disorders assessed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria was high in opiate-dependent treated persons (lifetime prevalence ranged from 26% to 35%). Among anxiety disorders, phobic disorders have been shown to often precede the onset of opiate dependence. The identification of substance-induced versus independent anxiety disorder has important treatment implication. The monitoring of anxiety symptoms after several weeks of abstinence may allow physicians to determine the relationship between dependence and anxiety and make a reliable diagnosis of any initial anxious disorder. Specific management of anxiety disorder may then be used.     

Utility of cyclodextrins in the formulation of genistein: Part 1. Preparation and physicochemical properties of genistein complexes with native cyclodextrins

Isoflavones are suitable guest molecules for inclusion complex formation with cyclodextrins (CDs). The molecular encapsulation with CDs results in a solid, molecularly dispersed form and in a significantly improved aqueous solubility of isoflavones. Genistein, a key isoflavone constituent of Ononidis spinosae radix was found to form a supramolecular, non-covalent inclusion complex with both β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD), while it did not form a stable complex with α-CD. The guest genistein was found to spatially located in the less polar cavity of cyclodextrin. The isolated binary genistein/CD complexes appeared novel crystalline lattices. The in vitro dissolution of genistein entrapped into both β- and γ-CD, significantly surpassed that of the plain isoflavone.     

Depressant effect of puromycin on the sympathetic ganglionic function : A study of the possible site and mechanism of action

The possible site and mechanism of action of puromycin (PU) on sympathetic ganglion isolated in vitro are investigated. We have observed that: (1) the depressant effect of PU on functional activity is higher on active than on resting ganglia; (2) PU interference with the divalent cations of the medium is negligible; (3) PU depresses the post-ganglionic action potentials to a higher extent than those recorded from preganglionic fibres; (4) synaptic potentials (recorded from curarised ganglia) are depressed to the same extent as post-ganglionic action potentials; (5) PU depresses the postganglionic response evoked by chemical stimulation with acetylcholine; (6) in the presence of PU, ganglia incubated with tritiated choline under sustained activity have a greater content of labelled acetylcholine. It is therefore suggested that PU exerts its action at both a pre- and a post-synaptic level.