New-generation azaindole-adamantyl-derived synthetic cannabinoids

Purpose

This work reports the synthesis and pharmacological and analytical data for a new series of recently identified azaindole-adamantyl-derived synthetic cannabinoids (SCs).

Methods

Each SC was synthesised using an efficient and divergent synthesis, and assessed by electron ionisation mass spectrometry (EIMS). The cannabimimetic activity of each compound was conducted using a fluorometric imaging plate reader (FLIPR) assay.

Results

The described EIMS method and retention time by gas chromatography were able to effectively differentiate each of the analogues regardless of the bicyclic core. For the first time in these SC structures, the bicyclic ring system was shown to have an impact on the cannabimimetic activities in the fluorometric assay of membrane potential. Analogues ranged from moderately potent at both CB₁ and CB₂ (e.g., AP4AIC EC₅₀?=?160 nM and EC₅₀?=?64 nM, respectively) to not active at either cannabinoid receptor (AP4AICA, AP5AICA, and APIC).

Conclusions

Further investigation into receptor selectivity surrounding these bicyclic cores could prove useful for future therapeutic applications.

     

Savings from generic drug substitution in the RSA--is its cost justified?

The causes of the recent rapid increases in health care costs in the RSA are briefly studied. Drug costs have increased largely through the use of new innovations, greater usage and price factors, but price increases have been below the rate of inflation. The savings in drug costs to be expected from the introduction of generic substitution have been calculated to be low in relation to overall health care costs, although of significance in relation to the survival of individual drug manufacturing businesses. The thrust towards generic substitution is possibly misplaced in that the potential savings in hospitalisation costs from the discovery of new drugs are so large that they justify the encouragement of the innovative drug manufacturers.     

The prevention of 'dry socket' with topical metronidazole in general dental practice

OBJECTIVE: The purpose of the study was to determine if the intra-alveolar application of topical metronidazole gel could reduce the incidence of alveolar osteitis (dry socket) following routine tooth extraction in molar and premolar extraction sites. DESIGN: This was a multicentre, double blind, randomised, placebo-controlled clinical trial. A total of 302 patients took part, of which 23 returned with alveolar osteitis. Of these, eight had received the metronidazole gel and 15 the placebo. SETTING: The study was carried out in three general dental practices by general dental practitioners working in England over the period 2000-2003. MAIN OUTCOME MEASURES: Following extraction of either a molar or premolar tooth, either a 25% metronidazole gel or KY Jelly was syringed gently into the socket. A painful post operative complication was recorded if either a dry socket was present or the patient returned with pain. RESULTS AND CONCLUSIONS: The difference in the incidence of alveolar osteitis between the placebo and the active gel groups was not significant and it was concluded that 25% topical metronidazole gel was not effective in reducing the incidence of alveolar osteitis. It was found that the incidence of alveolar osteitis reduced with increasing age and was more likely to occur in a patient with a previous history of the condition.     

HGV2009 meeting: bigger and better studies provide more answers and more questions

The 11th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2009: Tallinn, Estonia, 11th–13th September 2009) provided a stimulating workshop environment where diverse academics and industry representatives explored the latest progress, challenges, and opportunities in relating genome variation to evolution, technology, health, and disease. Key themes included Genome‐Wide Association Studies (GWAS), progress beyond GWAS, sequencing developments, and bioinformatics approaches to large‐scale datasets. Hum Mutat 31:1–3, 2010. © 2010 Wiley‐Liss, Inc.     

Reading the problem family: post-structuralism and the analysis of social problems

Post-structuralist theory questions the rational pursuit of an underlying 'truth' that often characterizes social scientific inquiry, proposing instead the simultaneous existence of multiple and often contradictory truths. The problem family can, from this perspective, only be known through the different discourses that produce it. This paper suggests some of the political advantages of developing methods of reading 'problems' related to drugs and alcohol. Without this critical attention to language, we risk perpetuating the ways in which problems are talked about and thought about. Drawing on examples from debates surrounding teenage pregnancy and youth drinking, the paper argues that post-structuralism allows us to analyse the specific ways in which professional discourses write social problems, and hence to own them and to re-write them.