Flupirtine protects both neuronal cells and lymphocytes against induced apoptosis in vitro: implications for treatment of AIDS patients.
In the present study we demonstrate that flupirtine, an already clinically used, centrally acting, non-opiate analgesic agent, protects rat cortical neurons against HIV-gp120 induced apoptotic cell death. The drug was active at concentrations between 1 and 10 microg/ml. Furthermore we show inhibition of in vitro induced apoptosis in human blood mononuclear cells, using flupirtine. Induced apoptosis in peripheral blood mononuclear cells from healthy individuals and HIV-1 infected patients was reduced to approximately 50% after in vitro preincubation with flupirtine at concentrations between 0.1 and 10 microg/ml. The anti-apoptotic effect of flupirtine was restricted to CD3+ lymphocytes and in particular to CD4+ cells. Flupirtine does not affect uninduced apoptosis in human lymphocytes in vitro. The selective potential of flupirtine to reduce apoptosis without influencing uninduced apoptosis may qualify this compound as a potential drug in the therapy of HIV-1 infected patients.
Müller
W E
WE
Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität Mainz, Duesbergweg 6, 55099 Mainz, Germany.
Dobmeyer
J M
JM
Dobmeyer
T S
TS
Pergande
G
G
Perovic
S
S
Leuck
J
J
Rossol
R
R