Biomedical subjects

Angela Alsasua

Publications and source records attributed to Angela Alsasua.

4 recordsLinked to original sources

PubMed2005

Structural-activity relationship study on C-4 carbon atom of the CB1 antagonist SR141716: synthesis and pharmacological evaluation of 1,2,4-triazole-3-carboxamides.

A series of 1,2,4-triazole-3-carboxamides has been prepared from alkyl-1,2,4-triazole-3-carboxylates under mild conditions. The ability of these triazoles to displace [3H]-CP55940 from CB1 cannabinoid receptor was measured. However, they showed only poor to moderate binding affinities, indicating that substitution of the C-4 pyrazole atom of the CB1 reference compound SR141716 by a nitrogen atom results in loss of affinity. Further investigations for functionality indicated that the compound 6a exhibited significant cannabinoid antagonistic properties in the mouse vas deferens functional assay. This leads us to the conclusion that 6a binds at a different CB1 binding site or at a new cannabinoid receptor subtype.

Animals↗

PubMed2004

Anandamide vehicles: a comparative study.

Among the studies that investigate the vasorelaxation induced by anandamide, one of the most frequent differences is the use of distinct solvents that could modify vascular function and explain the controversial results described. The aims of this study were: to evaluate the influence of different cannabinoid vehicles in vascular function of rat aorta, and to compare the vasorelaxation induced by anandamide dissolved in different vehicles. Vehicles were: ethanol (70%), Tween 80/ethanol (2:1 and 1:1), 1:1:18 (Tween 80/ethanol/saline) and dimethylsulphoxide (DMSO) 0.5%. All the vehicles tested, except DMSO 0.5%, modified the vascular and/or the endothelial function in rat aorta rings. Anandamide caused a time- and concentration-dependent vasorelaxation in all the experimental groups except in ethanol group, but the mechanisms involved in its vasorelaxation appear to be different depending on the vehicle used. The results obtained with vehicles containing Tween 80 suggest a non-endothelial component in the vasorelaxation caused by anandamide, while those obtained with DMSO at 0.5% suggest an endothelial component in this vasorelaxation.

Animals↗

PubMed2004

Discovery of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1h-1,2,4-triazole, a novel in vivo cannabinoid antagonist containing a 1,2,4-triazole motif.

A new series of 1,2,4-triazoles have been prepared and the evaluation of their cannabinoid properties have been carried out. Compound 8 showed cannabinoid silent antagonist activity in mouse vas deferens and guinea pig ileum preparations and in vivo assays (cannabinoid tetrad) in mouse. It did not have intrinsic activity in these bioassays, and therefore, it did not behave as a partial agonist or an inverse agonist.

Animals↗

PubMed2003

New benzimidazole derivatives: selective and orally active 5-HT3 receptor antagonists.

The synthesis of new 5-HT(3) receptor antagonists is an interesting field of research because of their wide therapeutic use. The aim of this work is to functionally characterise a new series of benzimidazole derivatives previously described. These compounds bind to 5-HT(3) receptors and have been evaluated using in vitro (rat tunica muscularis mucosae) and in vivo tests (Bezold-Jarisch reflex in rat and gastrointestinal motility and spontaneous motility in mice). Ondansetron and 1-[4-amino-5-chloro-2-(3,5-dimethoxyphenil)methyloxy]-3-[1-[2-methylsulfonylamino]piperidin-4-yl]propan-1-one hydrochloride (RS 39604) were used as well known 5-HT(3) and 5-HT(4) receptor antagonists. These benzimidazole derivatives have proved to be 5-HT(3) receptor antagonists. Interestingly, they are as active as ondansetron when they are intraperitoneally (i.p.) or orally (p.o.) administered and, in mice, they seem to induce fewer behavioural changes at similar effective doses than does ondansetron. The present results confirm the usefulness of the previously proposed pharmacophore and justify the interest in these new benzimidazole derivatives.

5-Hydroxytryptophan↗