Mauro Quartaroli

GV196771A, an NMDA receptor/glycine site antagonist, attenuates mechanical allodynia in neuropathic rats and reduces tolerance induced by morphine in mice

The effects of the N-methyl-D-aspartate (NMDA) receptor/glycine site antagonist, GV196771A (E-4,6-dichloro-3-(2-oxo-1-phenyl-pyrrolidin-3-ylidenemethyl)-1H-indole-2-carboxylic acid sodium salt), on mechanical allodynia and on tolerance to the antinociceptive effects induced by morphine were evaluated. Its antiallodynic properties were studied in a model of chronic constriction injury applied to rat sciatic nerve. GV196771A (0.3-10 mg/kg, p.o.) dose-dependently inhibited established mechanical allodynia when tested 14 or 21 days after nerve ligation. In the formalin test in mice, GV196771A (10 or 20 mg/kg, p.o.), administered for 8 days together with morphine 10 mg/kg, i.p. inhibited morphine tolerance development in both early and late phases of the test. This finding reinforces the key role of the NMDA receptors in the plastic event, such as allodynia, which develops in some conditions of painful neuropathy. Moreover, the capability to strongly reduce morphine-induced tolerance suggests that GV196771A could be an alternative agent for the treatment of difficult pain states not only when given alone, but also in combination, in order to prolong the analgesic effects of the opiates.

Headache and anxiety–depressive disorder comorbidity: the HADAS study

Psychiatric comorbidity (prevalence and types) was tested in a naturalistic sample of adult patients with pure migraine without aura, and in two control groups of patients, one experiencing pure tension-type headache and the other combined migraine and tension-type headaches. The study population included 374 patients (158, 110 and 106) from nine Italian secondary and tertiary centres. Psychiatric comorbidity was recorded through structured interview and also screened with the Mini International Neuropsychiatry Interview (MINI). Only anxiety and depression were investigated. Psychiatric disorders were reported by 49 patients (14.6%; 10.9% of patients with migraine, 12.8% of those with tension-type headache and 21.4% of those with combined migraine and tension-type headaches). The MINI interview detected a depressive episode in 59.9% of patients with migraine, 68.3% of patients with tension-type headache and 69.6% of patients with combined migraine and tension-type headaches. Depression subtypes were significantly different across groups (p=0.03). Anxiety (mostly generalised) was reported by 18.4% of patients with migraine, 19.3% of patients with tension-type headache, and 18.4% of patients with combined migraine and tension-type headaches. The values for panic disturbance were 12.7, 5.5 and 14.2, and those for obsessive–compulsive disorders were 2.3, 1.1 and 9.4% (p=0.009). Based on these results, psychopathology of primary headache can be a reflection of the burden of the disease rather than a hallmark of a specific headache category.

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.

Extracellular Matrix Gene Expression in the Left Ventricular Tissue of Spontaneously Hypertensive Rats

The aim of this study was to investigate the extracellular matrix gene expression in the hypertrophied left ventricular tissue of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, at early and mature ages. Interestingly, with age, a marked increase (+85% and +187% at 25 and 30 weeks of age, respectively, p < 0.01, vs 5 weeks) in matrix metalloproteinase-1 (MMP-1) mRNA levels in SHR and a progressive decrease (-50%, -70%, -78%, -70% at 10, 15, 25 and 30 weeks, respectively, p < 0.01, vs 5 weeks) in WKY were seen. Moreover, mRNA levels were significantly lower in SHR at 5 weeks. The analysis of mRNA expression for the tissue inhibitor of metalloproteinase-1 (TIMP-1) showed a significant increase in WKY (+44% and +44%, vs 15 and 25 weeks, respectively, p < 0.05), whereas there were no significant changes in SHR with development. At 30 weeks TIMP-1 mRNA levels were significantly reduced in SHR. Temporal trends of procollagen alpha1(I) and procollagen alpha1(III) mRNA levels were similar in both strains, but lower levels for procollagen alpha1(III) were found in SHR at 5 and 30 weeks. Although no significant differences were measured between the strains, mRNA levels for fibronectin were found decreased in WKY and increased in SHR with age. The results of the present study suggest an altered balance between collagen deposition and collagen degradation with development in this model of left ventricular hypertrophy and hypertension.