Influenza A(H1N1)pdm09 vaccination policies and coverage in Europe.

In August 2010 the Vaccine European New Integrated Collaboration Effort (VENICE) project conducted a survey to collect information on influenza A(H1N1)pdm09 vaccination policies and vaccination coverage in the European Union (EU), Norway and Iceland. Of 29 responding countries, 26 organised national pandemic influenza vaccination and one country had recommendations for vaccination but did not have a specific programme. Of the 27 countries with vaccine recommendations, all recommended it for healthcare workers and pregnant women. Twelve countries recommended vaccine for all ages. Six and three countries had recommendations for specific age groups in children and in adults, countries for specific adult age groups. Most countries recommended vaccine for those in new risk groups identified early in the pandemic such as morbid obese and people with neurologic diseases. Two thirds of countries started their vaccination campaigns within a four week period after week 40/2009. The reported vaccination coverage varied between countries from 0.4% to 59% for the entire population (22 countries); 3% to 68% for healthcare workers (13 countries); 0% to 58% for pregnant women (12 countries); 0.2% to 74% for children (12 countries). Most countries identified similar target groups for pandemic vaccine, but substantial variability in vaccination coverage was seen. The recommendations were in accordance with policy advice from the EU Health Security Committee and the World Health Organization.

CGS 10746B: an atypical antipsychotic candidate that selectively decreases dopamine release at behaviorally effective doses.

CGS 10746B, a benzothiadiazepine, has a behavioral profile in mice and monkeys similar to the atypical antipsychotic clozapine. Unlike clozapine, CGS 10746B suppresses dopamine neuron firing rates and, when administered at behaviorally effective doses by the oral or intraperitoneal route, decreases neostriatal dopamine release without changing dopamine metabolism or occupying D2 receptors. CGS 10746B is the first atypical antipsychotic candidate that selectively decreases dopamine release.

Typical and atypical antipsychotic occupancy of D2 and S2 receptors: an autoradiographic analysis in rat brain.

In thin sections of rat brain, [3H]spiperone binds to D2 sites in the basal ganglia (caudate-putamen, nucleus accumbens, olfactory tubercle) and S2 sites in the claustrum and motor cortex. The in vitro displacement of [3H]spiperone from these regions was quantified autoradiographically with the "atypical" neuroleptics clozapine and thioridazine, which ameliorate psychosis, a "typical" neuroleptic, haloperidol, which also induces extrapyramidal side effects, or with metoclopramide, which induces extrapyramidal side effects but is an ineffective antipsychotic. Whereas metoclopramide was equipotent at D2 sites, haloperidol was less potent and clozapine and thioridazine more potent by 2- to 3-fold at competing for D2 sites in the nucleus accumbens or olfactory tubercle than in the caudate-putamen. As measured autoradiographically or with tissue homogenates, clozapine, thioridazine, and five other atypical neuroleptics were 4- to 800-times more potent at competing for S2 sites in the frontal cortex than for D2 sites in the basal ganglia. A preference of atypical antipsychotics for D2 receptors in the nucleus accumbens and olfactory tubercle and for the S2 receptor may explain the relative lack of extrapyramidal side effects produced by these compounds.

Autoradiographic localization and pharmacology of unique [3H]tryptamine binding sites in rat brain.

The distribution and pharmacological specificity of [3H]tryptamine binding to coronal and horizontal sections of the rat brain were investigated with computer-assisted autoradiography. [3H]Tryptamine bound to brain regions with up to 58% specificity, as determined with 10 microM tryptamine as a displacer. The capacity (Bmax) of saturable [3H]tryptamine binding sites was greatest in the nucleus accumbens and claustrum (660-760 fmol mg protein-1), with intermediate binding site concentrations in hippocampus, septum, olfactory tubercle, frontal cortex, cingulate cortex and caudate-putamen. The phenylalkylamine, p-methoxyphenylpropylamine and the beta-carboline, harmaline, as well as 5-methyl-tryptamine, displaced [3H]tryptamine from each of these brain regions with a potency that approximated the 5-9 nM affinity (Kd) of [3H]tryptamine binding to each site. Only micromolar concentrations of serotonin displaced [3H]tryptamine, which did not bind to S1, S2, D1, D2 or alpha- or beta-adrenergic sites. The unique pharmacology and the regional overlap of [3H]tryptamine binding sites with dopaminergic nerve terminals in the nucleus accumbens and caudate-putamen suggest that tryptamine-containing neurons in the mammalian brain may modulate behavioral functions such as locomotion.