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.
NIH ExPorter
NIH ExPorter