RESUMEN
This study examined the effects of peripheral-type benzodiazepine receptors in the forced swimming test. PK 11195 (1-(2-chloro-phenyl)-N-methyl-N-(1-methylpropyl)-1-isoquinoline carboxamide) and Ro5-4864 (7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4-benzodiazepine-2-one) were i.p. injected in mice, according to an acute (1 or 24 h) and a repeated (14 days) schedule. Pretreatment with the agonist, Ro5-4864, significantly reduced immobility time 1 h after treatment but not 24 h after it, whereas the antagonist, PK11195, did not interfere with the test parameters. Nevertheless, PK11195 pretreatment inhibited the Ro5-4864 antidepressant-like effect. Animals repeatedly treated with Ro5-4864 had a similar profile of action with no sign of motor impairment or locomotor activation as evaluated in the rota-rod and open-field tests, respectively. Aminoglutethimide pretreatment, which blocks the early step of steroid synthesis, inhibited the antidepressant-like effect of Ro5-4864. The present findings suggest an antidepressant-like profile for the benzodiazepine, Ro5-4864, that seems to involve steroid synthesis as underlying mechanism.
Asunto(s)
Antidepresivos/farmacocinética , Benzodiazepinas/farmacocinética , Benzodiazepinonas/farmacocinética , Receptores de GABA-A/efectos de los fármacos , Natación , Aminoglutetimida/administración & dosificación , Aminoglutetimida/farmacocinética , Animales , Antidepresivos/administración & dosificación , Benzodiazepinas/administración & dosificación , Benzodiazepinas/antagonistas & inhibidores , Benzodiazepinonas/administración & dosificación , Agonistas de Receptores de GABA-A , Imipramina/administración & dosificación , Imipramina/farmacocinética , Inmovilización , Inyecciones Intraperitoneales , Isoquinolinas/administración & dosificación , Isoquinolinas/farmacocinética , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Sistema Nervioso Periférico/química , Prueba de Desempeño de Rotación con Aceleración Constante , Factores de TiempoRESUMEN
BACKGROUND: Substantial progress has been made in the treatment of acute myeloid leukemia in the last two decades. We wanted to evaluate the outcome of intensive chemotherapy and the influence of recent therapy changes in underprivileged patients treated in a large urban public university hospital. METHODS: The records of all patients treated for acute myeloid leukemia from 1980 to 1993 were analyzed. RESULTS: 109 patients were identified; 41 did not receive any treatment for the leukemia because of infectious and/or hemorrhagic complications of advanced disease. Median survival in this group was 4 days. The other 68 patients received one of two induction protocols: TAD from 1980 to 1985 (n = 23) and ara-C plus daunorubicin from 1985 to 1992 (n = 45). The complete remission rate was 56%, disease-free survival 24% and overall survival 15% at 13 years. Overall survival was better for patients treated with ara-C plus daunorubicin than with TAD (19% versus 8%, p = 0.01). This is attributed to a reduction in infection mortality after ceftazidime and amikacin replaced cephalotin, carbenicillin and amikacin as the antibiotic regimen. CONCLUSIONS: The most effective intervention in our population would probably be an improvement in the primary health care system, so that earlier diagnosis could allow the treatment of a larger fraction of patients.