Assessing mixed anxiety-depressive disorder. A national primary care survey.

Prevalence and risk factors associated with mixed anxiety-depressive disorder (MAD) have yet to be established. Using MINI 5.0.1 and HADS, a two-week survey involving 21,644 primary care patients was carried out. We found 1.8% of subjects with MAD and 20% of subjects with a co-morbid anxiety and depression (CAD) disorder. MAD patients without a past history of anxiety/affective episodes were defined as "pure MAD" (pMAD: 0.9% of the sample). While MAD patients showed a number of differences vs. the other groups of patients in the socio-demographic statistics, pMAD patients were not different, apart from a higher proportion of males vs. CAD patients. Nearly in all the comparisons, MAD and pMAD patients showed lower association with life events and with a familial predisposition than the other patients. On HADS assessment, MAD showed a higher risk of anxiety and depressive symptoms than anxiety diagnoses, a lower risk of depressive symptoms than depressive diagnoses and a lower risk of both anxiety and depressive symptoms than CAD. Since more than a half of MAD patients were classified as pMAD, the hypothesis that MAD should be viewed as a partial remission of a major depression is not entirely confirmed in our study.

Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in animal models of sustained inflammation and chronic neuropathic pain.

Chiral tetrahydroquinoline derivatives have been prepared by an asymmetric Mannich-type condensation reaction using commercially available vinyloxyethylsilane and a N-arylimino R-(+)-t-butyl lactate ester, in the presence of a catalytic amount of metal triflates as Lewis acids. This synthetic approach gave rise to the target aldehyde intermediate in moderate facial diastereoselectivity and in high chemical yield. This efficient route enabled to scale up the synthesis of an orally bioavailable glycine antagonist showing outstanding in vivo anti-hyperalgesic activity in different animal models of sustained inflammation and chronic neuropathic pain.

Synthesis and pharmacological characterisation of 2,4-dicarboxy-pyrroles as selective non-competitive mGluR1 antagonists.

Metabotropic glutamate receptors (mGluRs) are an unusual family of G-protein coupled receptor (GPCR), and are characterised by a large extracellular N-terminal domain that contains the glutamate binding site. We have identified a new class of non-competitive metabotropic glutamate receptor 1 (mGluR1) antagonists, 2,4-dicarboxy-pyrroles which are endowed with nanomolar potency. They interact within the 7 transmembrane (7TM) domain of the receptor and show antinociceptive properties when tested in a number of different animal models.