Potential anxiogenic effects of cannabinoid CB1 receptor antagonists/inverse agonists in rats: Comparisons between AM4113, AM251, and the benzodiazepine inverse agonist FG-7142

Cannabinoid CB1 inverse agonists suppress food-motivated behaviors, but may also induce psychiatric effects such as depression and anxiety. To evaluate behaviors potentially related to anxiety, the present experiments assessed the CB1 inverse agonist AM251 (2.0-8.0 mg/kg), the CB1 antagonist AM4113 (3.0-12.0 mg/kg), and the benzodiazepine inverse agonist FG-7142 (10.0-20.0 mg/kg), using the open field test and the elevated plus maze. Although all three drugs affected open field behavior, these effects were largely due to actions on locomotion. In the elevated plus maze, FG-7142 and AM251 both produced anxiogenic effects. FG-7142 and AM251 also significantly increased c-Fos activity in the amygdala and nucleus accumbens shell. In contrast, AM4113 failed to affect performance in the plus maze, and did not induce c-Fos immunoreactivity. The weak effects of AM4113 are consistent with biochemical data showing that AM4113 induces little or no intrinsic cellular activity. This research may lead to the development of novel appetite suppressants with reduced anxiogenic effects. © 2009 Elsevier B.V. and ECNP

Green transformations of bio-based chemicals

The thesis was focused on the development of green chemical technologies for the upgrading of platform molecules obtainable from renewable feedstocks. The platforms were chosen among those considered as the most promising for the development a new, sustainable, chemical industry. Levulinic acid was converted into compounds with a higher degree of oxygenation without actually using oxidizing agents. This was achieved by using dimehtyl carbonate (DMC), a green reagent and solvent, in basic catalysis. Bio-derived lactones (γ-valero-, γ-butyro-, δ-valero- and ε-capro-lactone) were reacted with three dialkylcarbonates (DMC, diethyl- and dibenzylcarbonate) to yield α-alkylated derivatives (from the 5-membered rings) or the highly oxygenated acyclic monomeric derivatives (from 6- and 7-membered rings). γ-valerolactone was used as a model to study acid catalysed ring-opening reactions. A novel reactivity was discovered in the presence of DMC; a mechanism was proposed. The 4-methoxy pentanoyl moiety was thus accessible by a green route. The reaction was then extended to a continuous flow process with solid acid catalysts. The selectivity towards the mentioned moiety or methyl pentenoate was tuned by optimising the parameters. Bio-derived diols were efficiently upgraded using organic carbonates in tandem with ionic liquids as organocatalysts. The study investigated the parameters that control the selectivity towards cyclic- or linear di-carbonates. The derivatisation of fatty acids methyl esters in conditions of on-water catalysis was investigated, aiming to develop a green strategy to reduce the cloud point of biodiesels. A new branched additive was synthesised, the thermal characteristics of which were analysed. The effect of reagents structure on on-water catalysis was investigated. The model reactions between cyclopentadiene and alkyl vinyl ketones allowed to demonstrate that little increases of the alkyl chain of a reactant have a dramatic influence on the catalytic effect