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Biomedical subjects

Sonia Martínez

Publications and source records attributed to Sonia Martínez.

7 recordsLinked to original sources
PubMed2005

Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking activity.

The synthesis and pharmacology of a new series of 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles that combine central serotonin (5-HT) reuptake inhibition with alpha(2)-adrenoceptor blocking activity is described as potential antidepressants. Four compounds were selected for further evaluation, and the combination of both activities was found to be stereoselective, residing mainly in one enantiomer. Reversal of the loss of righting induced by the alpha(2)-agonist medetomidine in rats confirmed the alpha(2)-adrenoceptor blocking activity in vivo and also demonstrated CNS penetration. Antagonism of p-chloroamphetamine (pCA)-induced excitation as well as blockade of the neuronal 5-HT depletion induced by p-CA administration in rats confirmed their ability to block the central 5-HTT, even after oral administration. Replacement of the oxygen atom at the 5-position of the tricyclic scaffold by a nitrogen or a carbon atom, as well as O-substitution at position 7, led also to active compounds, both in vitro and in vivo.

Administration, Oral↗
PubMed2005

Ethylene-styrene copolymerization with constrained geometry catalysts: a density functional study.

A density functional theory (DFT) study of the ethylene-styrene copolymerization process with titanium-based constrained geometry catalyst (CGC) is presented. To establish the difference between simplified CGC or real CGC models, i.e., considering all ligands of the catalyst, we have performed calculations for ethylene and styrene insertions in both models. Thus, we have used two different DFT functional, BP86 and B3L YP along with two basis set, LANL 2DZ (without polarization functions) and DZVP (including polarization functions). We have noted certain differences between theoretical results published by other authors and our theoretical and experimental data.

Journal Article↗
PubMed2005

8-NH2-boldine, an antagonist of alpha1A and alpha1B adrenoceptors without affinity for the alpha1D subtype: structural requirements for aporphines at alpha1-adrenoceptor subtypes.

Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human alpha (1A), alpha (1B) and alpha (1D) adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each alpha (1)-AR subtype. All the compounds tested competed for [ (125)I]-HEAT binding with steep and monophasic curves. The most interesting compound was 8-NH (2)-boldine, which retains the selective affinity for alpha(1A)-AR (pKi = 6.37 +/- 0.21) vs. alpha(1B)-AR (pKi = 5.53 +/- 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for alpha(1D)-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cortex confirms the results obtained for human cloned alpha (1)-AR subtypes. The compounds selective for the alpha (1A) subtype discriminate two binding sites in rat cerebral cortex confirming a mixed population of alpha (1A)- and alpha (1B)-AR in this tissue. All compounds are more selective as inhibitors of [ (3)H]-prazosin binding than of [ (3)H]-diltiazem binding to rat cerebral cortical membranes. A close relationship was found between affinities obtained for cloned alpha (1A)-AR and inhibitory potencies on noradrenaline-induced contraction or inositol phosphate accumulation in tail artery, confirming that there is a homogeneous functional population of alpha(1A)-AR in this vessel. On the contrary, a poor correlation seems to exist between the affinity of 8-NH (2)-boldine for cloned alpha (1D)-AR and its potency as an inhibitor of noradrenaline-induced contraction or inositol phosphate accumulation in rat aorta, which confirms that a heterogeneous population of alpha (1)-AR mediates the adrenergic response in this vessel.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2004

Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha2-adrenoceptor antagonistic activities. Part 2: Further exploration on the cinnamyl moiety.

In our previous paper we have described the synthesis of a series of 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, as novel dual 5-HT reuptake inhibitors and alpha2-adrenoceptor antagonists. That investigation led to the identification of the cinnamyl fragment as the most suitable moiety for combined activity. This paper outlines a further optimisation programme, focused on the exploration of the aromatic ring present on the cinnamyl moiety of compounds 1, 2 and 3.

Adrenergic Antagonists↗
PubMed2003

Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and alpha(2)-adrenoceptor antagonistic activities: a novel series of potential antidepressants.

The synthesis of a series of novel 3-piperazinylmethyl-3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles as novel dual 5-HT reuptake inhibitors and alpha(2)-adrenoceptor antagonists is described. Their affinity at the three different human alpha(2)-adrenoceptor subtypes and the 5-HT transporter site is reported. The in vivo activity of the compounds was measured in two different assays: (1). inhibition of pCA-induced excitation, which evaluates the ability to block the central 5-HT transporter, and (2). inhibition of xylazine-induced loss of righting, which evaluates the ability to block central alpha(2)-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed2002

Uptake of alpha-tocopherol by the mammary gland but not by white adipose tissue is dependent on lipoprotein lipase activity around parturition and during lactation in the rat.

This study was undertaken to test the potential role of changes in lipoprotein lipase (LPL) activity in the mammary gland and adipose tissue around parturition and lactation on the uptake of alpha-tocopherol in the rat. Plasma levels of alpha-tocopherol and triglycerides were higher in 20-day pregnant rats than in virgin rats, whereas its concentration was higher in the mammary gland of the former, and no differences were detected in adipose tissue between the groups. After an oral alpha-tocopherol and triglyceride load, both appeared in plasma faster in pregnant rats than in virgin rats, the change being even faster for alpha-tocopherol than for triglycerides. After 24 hours, both alpha-tocopherol and triglycerides in d < 1.006 lipoproteins were higher in pregnant rats than in virgin rats, LPL activity was higher in the mammary gland, and lower in adipose tissue in the former, whereas alpha-tocopherol concentration also appeared higher in the mammary gland of pregnant rats, and no differences were detected between the groups in adipose tissue. At day 13 of lactation, an oral load of alpha-tocopherol and triglycerides caused a higher increase of plasma alpha-tocopherol levels than triglycerides, and this effect decreased when rats had their litter removed 48 hours before analysis. In these litter-removed rats, the appearance of alpha-tocopherol and triglycerides in plasma was higher in d < 1.006 lipoproteins than in lactating rats. Also, both LPL activity and alpha-tocopherol concentration in the mammary gland plus milk was lower in litter-removed rats than in the lactating rats, whereas LPL in adipose tissue was higher in the former, although no difference in alpha-tocopherol was found. Thus, data are consistent with the role of LPL activity in the mammary gland modulating the uptake of alpha-tocopherol during pregnancy and lactation, although this is not true in adipose tissue.

Adipose Tissue↗