The analgesic effect of gemcitabine in mice.
The analgesic effect of gemcitabine was analyzed in two experimental tests in mice. In the first test gemcitabine produced a dose-dependent decrease of the number of torsions produced by i.p. acetic acid in mice proving an analgesic effect. In the hot plate test the gemcitabine produced a non-statistical significant increase of the latency of the leakage, but a statistically significant increase of the latency of the salt proving an analgesic effect produced especially by a nervous central mechanism like morphine. The association of the gemcitabine and morphine proved that an inactive dose of gemcitabine increased statistically significant the effect of morphine proving a potentiation of the effect of morphine by gemcitabine. A same potentiation was demonstrated also by an effective analgesic dose of gemcitabine. The analgesic effect of the gemcitabine was antagonized by aminophiline, an inhibitor of the phosphodiesteraze, proving that the analgesic effect of the gemcitabine could be produced by a decrease of the intracellular cAMP. According to the chemical structure of gemcitabine it is possible that gemcitabine decrease the velocity of the degradation of the GMP fixed on the alpha subunit of the Gi protein and so increase the effect of the activated a subunit of the Gi protein to inactivate the adenylatecyclase. The analgesic effect of gemcitabine could be important in clinical management of antineoplastic patient by increasing the quality of life of these patients and the property of gemcitabine to potentiate the analgesic effect of morphine could be important by decreasing the needs of morphine of the antineoplastic patients. More researches will be necessary for evaluating also other nervous central effects of gemcitabine, for evaluation if other antineoplastic drugs have the same effect and for establishing a possible chemical structure-analgesic effect relationship and maybe also for evaluation if other effects of morphine are potentiated by gemcitabine and other antineoplastic drugs.
Fulga
Carmen
C
N. Gh. Lupu Institute of Internal Medicine, Colentina Hospital, Bucharest, Romania. carmenfulga@yahoo.com
Zugravu
A
A
Fulga
I
I
D019342:Acetic Acid; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D051379:Mice; D017288:Pain Threshold / Q000187:drug effects* / Q000523:psychology; D011930:Reaction Time; D000093542:Gemcitabine
D003841:Deoxycytidine; D019342:Acetic Acid; D000093542:Gemcitabine