[en] The recent tomography status using radiopharmaceuticals have been contributing greatly with the 'age of certainty' in the diagnosis examination of syndromes, pathologies and clinical signs, because they can evidence some phenomena occurring in a molecular manner. The purpose of this work have had the development of new diaminodithiol (DADT) perfusion radiopharmaceuticals to be used in brain diagnosis using S.P.E.T. (Single Photon Emission Tomography). Initially, the rational planning had been performed with the new DADT molecular structures as radiopharmaceutical candidates. Using of Q.S.A.R. (Quantitative Structure Activity Relationship) techniques, the molecular descriptors such as partition coefficient and effective polarizability, have been studied in order to increase the blood brain barrier transport and the brain uptake respectively. Applying the Q.S.P.R. (Quantitative Structure Property Relationship) concepts to perform drug latentiation, based on bio-labile functional groups, the congener DADT derivative has been transformed into a pro-drug that works as a DADT moiety carrier, allowing the increasing of brain radiopharmaceutical uptake. Later on, synthetic routes and chemical purifications have been developed allowing the creation of the proposed chemical structure. Each new DADT derivative has been synthesized and analyzed in terms of elemental analysis, infrared and NMR spectra, in order to confirm its proposed chemical structure. Then, the new derivative has been labeled with ^99mTc, radiochemically purified, intravenously injected in Swiss mice, allowing its biodistribution to evidence its brain transport and uptake. The rational planning studies have been re-evaluated after each biodistribution had been performed, to see what kind of molecular descriptor was responsible for causing a stronger optimization in the brain perfusion characteristics and then, new DADT derivatives have been prepared. Three new DADT derivatives have been obtained by using QSAR: DADT-PR, DADT-DIPA, DADT-DIB. In terms of absolute values, expressed as % dose/organ, the DADT-DIPA showed the biggest brain uptake, because it has got the partition coefficient closest to the ideal and a high effective polarizability value. DADT - DIPA proved that the partition coefficient is the most important molecular descriptor in the optimization of the DADT derivatives because in the case of DADT-DIB, even possessing the most effective polarizability, but a non-ideal partition coefficient value , it was showed a significantly smaller brain uptake. The DADT -DIPA derivative is potentially a brain perfusion radiopharmaceutical to be explored in details. The DADT - BUT , developed by QSPR despite the fact of having a low brain uptake expressed in terms of % dose/organ, presented pro-drug behaviour, because even 30 minutes after its administration, the radiopharmaceutical strikingly still retained 62% of the 5 minutes brain uptake. This DADT derivative has proved to possess low cerebral clearance, creating the possibility of becoming a good brain perfusion agent, once its structure assumes the closest to ideal partition coefficient value by adequate molecular modification. (author)

[en] Polarizability correlates well with organic ion stabilization in solution and can be defined as a measure of the relative ease of the distortion of the electronic cloud of a dipolar system exposed to an external electric field. The effective atomic polarizability, α_d, has a fundamental influence on chemical reactivity in the gas phase and in solution. In terms of chemical reactivity the charge is generated within the molecule as a positive charge due to protonation, ionization or resulting from the attack of a nucleophilic anion. In this paper, lipoidal diaminedithiol (DADT) perfusion radioligands based on ⁹⁹Tc^m and possessing an alkylamine side chain have been used to check the influence of α_d on their brain uptake. Some new DADT derivatives, respectively DADT-DIPA (diaminedithiol-diisopropylamine), DADT DIBA (diaminedithiol - diisobutylamine), DADT-PR (diaminedithiol-branched piperidine), have been designed to have high nitrogen alkylamine α_d values. In spite of the fact of higher α_d values having been correlated to higher brain uptakes, there is not a clear mechanism able to trap these radioligands into the brain space. (author)

[en] S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl β-cyclodextrin (HP-β-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-β-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-β-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment. (author)

[en] Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with β-cyclodextrin (β-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:β-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:β-CD. DOSY-NMR shows that the association constant is 55.5 M^-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of β-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment. (author)