I. W. Waters

Lethal synergism of phencyclidine with a precursor and contaminant, 1-piperidinocyclohexanecarbonitrile

Abstract The acute median lethal dose (LD50) was determined in rats (p.o.) and mice (i.p.) for phencyclidine (PCP) or 1-piperidinocyclohexanecarbonitrile (PCC) individually and in combination. The LD50 (mg/kg) of PCP was 2.3 or 2.5 times higher than the LD50 of PCC in mice or rats, respectively. For mice, combinations (8:1 or 4:1) of PCP + PCC showed additive synergism, while in rats a 2:1 combination caused sub-additive synergism. Dogs receiving an intravenous infusion of PCP + PCC (4:1) died at a one-third lower dosage of PCP than when PCP was given alone. Prior treatment with NaNO2 significantly elevated the i.p. LD50s in mice for PCC alone or PCP + PCC (3:1) as it did for KCN. These data support the inference that toxicity from PCC arises primarily from the cyanide ion which it releases. The possibility of a toxic synergism in the course of human exposure to PCC-contaminated “street PCP” is raised.

Acute phencyclidine poisoning in the unanesthetized dog: Pathophysiologic profile of acute lethality☆

Phencyclidine HCl was infused intravenously (1.0 mg/kg/min) to unanesthetized mongrel dogs until death. All animals experienced tonic-clonic convulsions (mean convulsive dose: 4.7 +/- 0.3 mg/kg) which lasted until shortly before death (mean lethal dose: 49.8 +/- 2.5 mg/kg). Significant increases in heart rate, arterial blood pressures, cardiac output, body temperature, and arterial pCO2 were observed in all animals. Significant reductions from pre-drug control values were observed in total peripheral resistance, arterial pH, arterial pO2, and respiratory minute volume. Blood lactate, oxygen uptake, and plasma glucose levels rose to values significantly higher than pre-drug control values then declined during the latter phase of the experiment, glucose levels decreased to final values lower than control. Animals appeared to die of primary respiratory failure, which was exacerbated by hyperthermia, and which resulted in final cardiovascular collapse.