RESUMEN
Clonidine (0.01 to 0.16 mg/kg) and lofexidine (0.01 to 0.64 mg/kg) produced a dose-dependent inhibition of diarrhea induced by castor oil treatment in the rat. Both drugs were more potent and longer acting than diphenoxylate. Pre- and posttreatment with naloxone (5 mg/kg) failed to prevent or antagonize the antidiarrheal effect of clonidine and lofexidine. These data suggest that clonidine and lofexidine may provide potent antidiarrheal activity of a nonnarcotic nature.
Asunto(s)
Antidiarreicos , Clonidina/análogos & derivados , Clonidina/uso terapéutico , Diarrea/tratamiento farmacológico , Animales , Clonidina/administración & dosificación , Masculino , Narcóticos , RatasRESUMEN
Co-administration of desipramine and fluoxetine resulted in a 27% decline in cerebral cortical beta-adrenoceptor density after four days - a time point at which neither agent alone was effective. After 14 days, desipramine- and desipramine + fluoxetine-treated rats showed decreased receptor levels, with a greater decrement seen with the combined treatment. Fluoxetine, alone, had no affect on beta-adrenoceptor density at any time point examined. These effects are attributable to central serotonergic action since they were prevented by prior treatment with p-chlorophenylalanine. Cyproheptadine, a 5-HT2 antagonist, did not block these effects. Independent administration of fluoxetine and desipramine produced approximately 20% decrement in isoproterenol-stimulated cyclic AMP accumulation after four days of treatment. Co-administration of desipramine and fluoxetine resulted in a 35% decrement in cyclic AMP accumulation which was nearly additive with that produced by either drug alone. Consequently, the combination of a norepinephrine and serotonin uptake inhibitor may be an advantageous and rapid treatment for the alleviation of certain forms of depression.
Asunto(s)
Desipramina/farmacología , Fluoxetina/farmacología , Receptores Adrenérgicos beta/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , AMP Cíclico/metabolismo , Dihidroalprenolol , Ácido Hidroxiindolacético/metabolismo , Técnicas In Vitro , Masculino , Ratas , Ratas Endogámicas , Serotonina/metabolismoRESUMEN
Discontinuation of chronic morphine infusion in rats resulted in the reliable occurrence of withdrawal body shakes. This sign of narcotic withdrawal was dose-dependently reduced by lofexidine (0.04-0.64 mg/kg) and clonidine (0.01-0.16 mg/kg). As with clonidine, the activity of lofexidine was not prevented by naloxone (5 mg/kg). In addition, diarrhea induced by naloxone (5 mg/kg) in morphine dependent rats was also prevented by lofexidine or clonidine pretreatment. These data suggest that lofexidine, like clonidine, may reduce the narcotic withdrawal syndrome in humans.