effects of atropine and methylatropine on erythropoietin production and hypothalamic stimulation in rabbits

A atropina bloqeia parcialmente o aumento na produção de EPO em coelhos submetidos a hipóxia. Na tentativa de estudar a possibilidade do envolvimento de mecanismos colinérgicos no controle da eritropoiese, a metilatropina foi administrada a coelhos, que, em seguida, foram submetidos a hipóxia hipobárica ou a estimulação do hipotálamo posterior. A metilatropina não bloqueou o aumento na produção de EPO em resposta à hipóxia, nem o aumento na taxa de reticulócitos na circulação periférica. A antropina, que atravessa a barreira hematoencefálica, bloqueia tanto o aumento na produção de EPO, quanto o aumento no número de reticulócitos na circulação periférica

Substituded pyrazolylhydrazones: a new class of platelet aggregation inhibitors

A series of 5-pyrazolylhydrazone derivates (I) were designed to be mixed hybrid isosteres of both BW-755C and CBS-1108 which belong to the class of dual cyclooxygenase and 5-lipoxygenase inhibitors. Pharmacological evaluation of some members of this series (Ia, 1-formy 1-3,4-methylenedioxy-6-nitrobenzene-5-(1-phenyl-3-methyl-4-nitropyrazolil)hydrazone; Ib, 2-formylfurane-5-(1-phenyl-3-methyll-4-nitropyrazolyl)hidrazone; Ic, (E)-2-(formylethenylfurane)-5-(1-phenyl-3-methyl-4-nitropyrazolyl)hydrazone showed that they inhibit the in vitro platelet aggregation of citrated platelet-rich rabbit plasma induced by ADP (5µM), collagen (5µg/ml) and arachidonic acid (100 µM). Compounds Ia and Ic at 100 µM concentration showed 49% and 58% inhibition, respectively, of ADP-induced aggregation. In the arachidonic acid-induced aggregation, compounds Ia and Ib at 100 µM concentration fully inhibited platelet aggregation. All compounds significantly inhibited the collagen-induced aggregation. In contrast, indomethacin (10 µM) showed 100% and 85% aggregation inhibition against arachidonic acid and collagen, respectivelym, and was inactive in the ADP- induced aggregation test. These results suggest that the structure-activity relationship in this series of compounds is dependent on the hydrazone moiety at position 5 of the pyrazole ring and on the distance between the aryl ring and the pyrazole ring and that the 2-furyl ring is at the optimal distance for the maximal activity