Chronic anti-phencyclidine monoclonal antibody therapy decreases phencyclidine-induced in utero fetal mortality in pregnant rats.
J J Hubbard, E M Laurenzana, D K Williams, W B Gentry, S M Owens
International Immunopharmacology December 2011 DOI: 10.1016/j.intimp.2011.09.016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment (pregnant rat model) Peer reviewed |
|---|---|
| Sample size | 5 |
| Population | Pregnant Sprague-Dawley rats (n=4-5 per group) studied from gestation days 6-21 |
| Intervention | Phencyclidine (PCP) |
| Dose | PCP 1 mg/kg intravenous bolus; mAb6B5 45 mg/kg |
| Duration | Multiple days during pregnancy; measurements from gestation days 6-21 |
| Measures | Litter size, number of live vs. dead pups, maternal blood pressure and heart rate (radiotelemetry with femoral arterial pressure catheter), locomotor activity |
| Key findings | Anti-PCP monoclonal antibody mAb6B5 significantly reduced PCP-induced fetal deaths in utero (odds ratio 3.2, 95% CI 1.3 to 7.9) and reduced acute PCP-induced maternal locomotor effects in the second trimester, while maternal blood pressure and heart rate responses to PCP were not significantly affected. The authors suggest antibody treatment during pregnancy can safely protect mother and fetus from PCP-related harm even at a dose too low to block other maternal effects. |
Abstract
Illicit drug use during pregnancy is a serious social and public health problem inflicting an array of deleterious effects on both mother and offspring. We investigated the hypothesis that a murine anti-phencyclidine (PCP) monoclonal antibody (mAb6B5; K(D)=1.3 nM) can safely protect mother and fetus from PCP-induced adverse health effects in pregnant rats. Pregnant Sprague-Dawley rats (n=4-5) were intravenously administered bolus injections of PCP (1mg/kg) on multiple days during pregnancy. They were also chronically treated with anti-PCP mAb6B5 at 45 mg/kg as a PCP antagonist. This dose provided one mAb-PCP binding site for every four PCP molecules. Therapeutic and safety study endpoints included pregnancy outcome (litter size, number of live vs. dead pups), maternal hemodynamic status and locomotor activity. Maternal hemodynamic changes (i.e., blood pressure and heart rate) and locomotor activity were measured in dams from gestation days 6-21 (one day antepartum) using a radiotelemetry-tracking device with a femoral arterial pressure catheter. This mAb6B5 treatment regimen significantly (p=0.008) reduced the number of PCP-induced in utero fetal deaths (odds ratio=3.2; 95%CI 1.3 to 7.9) and significantly (p<0.05) reduced acute PCP-induced maternal locomotor effects in the second trimester. Maternal hemodynamic responses to PCP were not significantly affected by mAb6B5 treatment. In conclusion, these data suggest that anti-PCP mAb treatments administered during pregnancy can safely protect a mother and her fetus(es) from PCP-related morbidity and mortality even when the mAb dose is too low to significantly prevent other PCP-induced maternal pharmacological effects.