Drug abuse by pregnant women is a major health concern with limited treatment options. The objective of this project is to determine if a monoclonal antibody medication can protect mothers and their fetuses from the adverse effects of phencyclidine (PCP) abuse. Pre-clinical pharmacological studies in pregnant rats will accomplish this objective by measuring the ability of this anti-PCP monoclonal antibody (designated mAb6B5) to protect mothers and their fetuses from PCP-induced injury. Previous pre-clinical studies showed that a single, low dose (15 mg/kg) of anti-PCP mAb6B5 dramatically decreased brain PCP concentrations and PCP-induced adverse health effects in male rats for prolonged periods (at least 2 weeks). This proposal hypothesizes that anti-PCP mAb6B5 could safely protect the maternal-fetal unit from PCP pharmacological effects. These studies will investigate this hypothesis by measuring the pharmacokinetics and cardiovascular pharmacodynamics of PCP and anti-PCP mAb6B5 in the maternal-fetal unit using a rat model of pregnancy.
The specific aims are: (1)-to investigate the safety/efficacy of anti-PCP mAb6B5 maintenance treatment of CHRONIC PCP infusion during pregnancy by measuring PCP and anti-PCP mAb6B5 pharmacokinetics in pregnant rats, (2)-to determine the cardiovascular pharmacodynamics of anti-PCP mAb6B5 treatments during chronic PCP exposure using radiotelemetry to monitor heart rate and blood pressure in freely moving pregnant rats, (3)-to establish the pharmacokinetics and cardiovascular pharmacodynamics of anti-PCP mAb6B5 treatment in a model of ACUTE, binge PCP abuse during pregnancy. These novel and innovative studies will be an important contribution to pre-clinical justification for the use of monoclonal antibodies as pharmacokinetic antagonists to protect both the mother and her fetus from the dangerous health effects of stimulant drugs of abuse. ? ? ?
| Hubbard, Jonathan J; Laurenzana, Elizabeth M; Williams, D Keith et al. (2011) The fate and function of therapeutic antiaddiction monoclonal antibodies across the reproductive cycle of rats. J Pharmacol Exp Ther 336:414-22 |
| Hubbard, J J; Laurenzana, E M; Williams, D K et al. (2011) Chronic anti-phencyclidine monoclonal antibody therapy decreases phencyclidine-induced in utero fetal mortality in pregnant rats. Int Immunopharmacol 11:2181-7 |
