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The levels of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF) and bisphenol S (BPS) were monitored in twenty-three samples of canned legumes from popular brands marketed in Italy. BPB, BPS and BPF were not detected in any samples, while BPA was found in 91 % of the samples in the concentration range 1.51-21.22 ng/mL. The risk associated with the human exposure to BPA was categorized using the Rapid Assessment of Contaminant Exposure (RACE) tool promoted by the European Food Safety Authority (EFSA). The results showed that there is no risk for any of the population groups when the current TDI value for BPA of 4 μg/kg bw/day was used as toxicological reference point. In contrast, using the new TDI value for BPA of 0.04 ng/kg bw/day, proposed by EFSA in December 2021, the existing risk was found to be real for all population groups.

The chemical modification of the molecular structure of psychoactive substances is a very common practice in the illicit drugs market, to by-pass current regulations; this lead to the production of compounds, known as "designer drugs", with the same or greater pharmacological effects of the parent drug. The phenomenon is also favored by the fact that the new synthetic compounds are not considered illegal by existing legislation. Amphetamine derivatives represent one of the largest classes of designer drugs. Generally, in toxicological laboratories, rapid screening tests are used for a first monitoring of drugs abuse. However, the available immunoassays for this class of substances are designed for amphetamine, methamphetamine and methylenedioxymethamphetamine, and generally they are unable to detect various amphetamine analogues. This can constitute a disadvantage because it can generate a great number of false-negative results. The present review aims to provide an overview of the cross-reactivity studies carried out on commercially available immunoassays to identify the presence of amphetamine derivatives in biological samples. The knowledge of cross-reactivity data makes it easier to interpret analytical results by demonstrating that a negative result does not always indicate the non-consumption of an amphetamine derivative. This review highlights the great need for more comprehensive screening immunoassays to use when analyzing biological matrices for drugs of abuse search, specifically for the more recent designer drugs..

N-Palmitoylethanolamide (PEA) is emerging as a novel therapeutic agent in the treatment of neuropathic pain and neurodegenerative diseases. Unfortunately, PEA poorly reaches the central nervous system (CNS), after peripheral administration, since it is inactivated through intracellular hydrolysis by lipid amidases. Since prodrug approach is one of the most popular methods used to increase cell permeability, the aim of this paper consists in the synthesis of a new galactosyl prodrug of PEA, the palmitoylethanolamide-succinamyl-D-galactos-6'-yl ester (PEAGAL). Biological experiments both in neuroblastoma and in C6 glioma cells, together with quantitative analyses performed through a LC-MS-MS technique, demonstrate the better efficacy of PEAGAL compared to PEA and its higher cell permeation. Our results encourage further experiments in animal models of neuropathic pain and of neurological disorders and/or neurodegenerative diseases, in order to promote a more effective peripherally administrated derivative of PEA.

Pathological conditions, such as Parkinson's disease and attention deficit hyperactivity disorder, have been linked to alterations of specific dopamine (DA) pathways. However, since exogenous DA does not cross the blood-brain barrier, DA levels can be modulated e.g. by DA precursors or DA reuptake blockers. Hereby histochemical, analytical and behavioral evidence shows that a galactosylated form of DA (GAL-DA) carries DA into the brain, thus modulating activity and nonselective attention in rats. To this aim adult male rats of the Naples high-excitability (NHE) and random bred controls (NRB) lines were given a single i.p. injection of GAL-DA (10 or 100 mg/kg). Three hours later the behavior was videotaped and analyzed for horizontal activity, orienting frequency and scanning duration. The dose of 100 mglkg of GAL-DA reduced by 25% the horizontal activity in NHE rats, mainly in the first part of the testing period. No effect was observed on orienting frequency or on scanning duration. However, GAL-DA 100 mg/kg was associated with longer rearing episodes in the second part of the testing period in NHE rats. In parallel experiments histochemistry with a galactose-specific lectin showed 10% increase in galactose residues into the striatum between 0.5 and 3.0 h. To quantify the level of GAL-DA, its metabolite DA-succinate and DA in the prefrontal cortex, neostriatum, and cerebellum, rats were killed 2.0 h after the injection of prodrug. Mass high performance liquid chromatography (HPLC) was used for analysis of GAL-DA and DA succinate whereas electrochemical HPLC for DA. Both HPLC techniques demonstrate that GAL-DA carries and releases DA into the brain. Specifically 100 mg/kg of GAL-DA increased DA level in the striatum in the NHE rats only. Moreover, DA in the mesencephalon (MES) was correlated positively with striatal and prefrontal cortex DA in NHE rats. In contrast DA in the MES was negatively correlated with striatal DA in NRB. GAL-DA disrupted these correlations in both rat lines. Thus, this new DA prodrug may modify DA neurotransmission and might have a potential clinical application.

New glycosyl derivatives of 3'-azido-3'-deoxythymidine (AZT) (1 and 2) were synthesized in order to improve AZT retention in the blood and to guarantee its sustained release, overcoming the necessity of multiple drug administrations. The esters synthesized (1 and 2) link AZT, by a succinyl linker, to the C-3 position of glucose and to C-6 of galactose. Furthermore, the chemical and enzymatic stabilities of esters 1 and 2 were evaluated in order to determine both their stability in aqueous medium and their feasibility to undergo enzymatic cleavage by esterase to regenerate the original drug. The pharmacokinetic profiles of esters 1 and 2, obtained after systemic administration, showed an interesting controlled release, in particular for ester 2, compared to the pharmacokinetic profile of AZT.

The synthesis of a series of 2-phenyl- and 2-(p-chlorophenyl)imidazo[1,2-a]pyrazine-3-carboxylic esters and acids is described. The structures of the new compounds were supported by 1H- and 13C-NMR spectra. These compounds were evaluated in vivo for their antiinflammatory and analgesic activities as well as for their ulcerogenic potential. Acids 8c and 8e were found to be the most potent antiinflammatory agents ( ⋍ 1 8 × indomethacin ), while 8a, 8d and 8f displayed analgesic activity ( ⋍ 1 16 × indomethacin ). The inhibitory activity on cyclooxygenase action was evaluated in vitro and discussed in comparison with results obtained in vivo.