Effect of neuroleptics on foot-pedal self stimulation from the ventral tegmentum mesencephali in rats and its correlation with cataleptogenic action

Experiments on rats have shown that droperidol, fluorophenazine, haloperidol, triphtazine, aminazin, thioridazin and clozapin are capable to reduce pedal self-stimulation from the ventral tegmen of the midbrain, which is not related to the cataleptogenic action of the neuroleptics or to their effect on the actuating motor mechanisms but is a consequence of the action on the emotional-positive reinforcement system. A significant positive correlation was disclosed between the ability of the neuroleptics given in effective doses to reduce pedal self-stimulation from the ventral tegmen and their cataleptogenic action.     

Clinical pharmacokinetics of vinca alkaloids

Vinca alkaloids (VA) represent a family of closely related molecules, which includes vincristine (VCR), vinblastine (VLB), vindesine (VDS) and navelbine (NVB), a new synthetic VA presently in phase II clinical trial. Development of sensitive and specific analytical tools (polyclonal and monoclonal antibodies) enabled us to investigate the kinetic behavior of VDS and NVB after IV bolus or long term administration. Following IV bolus injection, the mean pharmacokinetic parameters are: total plasma clearance: 0.53 l/h-1kg-1, 0.72 l/h-1kg-1 and apparent elimination half-life: 23.2 h, 39.5 h for VDS and NVB, respectively. Chronic treatment reveals time- and dose-dependence relationships and detailed observations of individual kinetics demonstrate an important interindividual variability for both drugs. Renal excretion of VDS and NVB is low (from 5 to 12% of the total dose), suggesting the important role of the liver in their rapid elimination.