Biomedical subjects

María Isabel Martín

Publications and source records attributed to María Isabel Martín.

5 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↗

PubMed2005

A cannabinoid agonist, WIN 55,212-2, reduces neuropathic nociception induced by paclitaxel in rats.

Paclitaxel is an effective antineoplastic drug treatment used as an anti-tumoral therapy. Unfortunately its use is associated with unwanted side effects, which include the development of peripheral neuropathies and neuropathic pain, greatly affecting the quality of life of patients. It is well known that agonists of the cannabinoid receptor are able to reduce hyperalgesia and allodynia that develop after nerve injury. Our aim was to evaluate the efficacy of the cannabinoid agonist WIN 55,212-2 to reduce the thermal hyperalgesia and the tactile allodynia induced by administration of paclitaxel in rats. Present results demonstrate that WIN 55,212-2 (1 mg/kg i.p.) significantly reduced the heat (P<0.0001) and the mechanical (P=0.0003) withdrawal thresholds, the dose being smaller than that required to reach similar effects in the sciatic nerve constriction model (1.5 mg/kg). When the cannabinoid tetrad test was evaluated to measure behavioral modifications, it was found that WIN 55,212-2 (1mg/kg) did not induce changes either in body temperature or in immobility time, and only a reduction in spontaneous motility was recorded. This effect was antagonized by SR 141716A, suggesting the involvement of the CB1 receptor, although the participation of CB2 receptors cannot be excluded from this study. When WIN 55,212-2 was administered intraplantar, no differences were observed between the injected paw and the contralateral paw, suggesting that systemic mechanisms are needed to reach effectiveness. From these results we suggest that cannabinoids may be an interesting alternative to reduce neuropathic symptoms induced by paclitaxel, however more work is required to assess this possibility.

Analgesics↗

PubMed2005

Evaluation of the effect of age on cannabinoid receptor functionality and expression in guinea-pig ileum longitudinal muscle-myenteric plexus preparations.

Cannabinoid drugs exert a wide range of biological effects and are currently under study for their multiple potential therapeutic uses. Cannabinoids reduce gastrointestinal (GI) motility and this is mediated by the CB1 cannabinoid receptor (CB1R) present in the myenteric neurones. GI motility can also be affected by a variety of pathophysiological situations, including ageing. The purpose of this work was to study the influence of age on the functionality and expression of CB1R in the myenteric plexus. Ileal longitudinal muscle-myenteric plexus (LMMP) preparations from young, adult and old guinea-pigs were used in two sets of experiments: in vitro assessment of the inhibitory cannabinoid effect upon electrically stimulated contractions and immunohistochemical quantification of myenteric neurones expressing CB1R. LMMP preparations responded to the synthetic cannabinoid WIN 55,212-2, and the endogenous cannabinoid ligand anandamide in an age-independent manner. The total number of CB1R-immunoreactive (IR) myenteric neurones, which included at least part of the motor neurones to the longitudinal smooth muscle, decreased in proportion to the general neuronal population; however, the proportion of CB1R-IR neurones was preserved in old animals. These data may justify the preservation of the effectiveness of the cannabinoids in the isolated guinea-pig ileum. This age-related independency of CB1R expression and effect on GI motility could be of interest if cannabinoids are to be used therapeutically.

Aging↗

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↗

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↗