Persistence of phencyclidine (PCP) and metabolites in brain and adipose tissue and implications for long-lasting behavioural effects.

PCP and its new metabolites persisted for very prolonged periods in rat brain and adipose tissue after a single 25 mgkg-1 intraperitoneal injection and showed accumulation after multiple dosing. The brain to plasma ratios for PCP between 0.5 h to 48 h after injection ranged between 6 to 8.8 and adipose tissue to plasma ratios between 31 to 113. The concentrations of metabolites of PCP in rat brain (ng-eqt/g. tissue) 1, 2 and 3 weeks after a single 25 mgkg-1 i.p. injection of PCP were approximately 390, 230 and 74 respectively and those of PCP 12, 6 and 5 ng/g. respectively. The long sojourn of PCP in adipose tissue and relatively slow egress therefrom explains cumulative effects upon multiple dosing and raises the possibility of mobilisation or release of large amounts of drug from fat stores in situations involving food deprivation, marked weight loss or stress. The persistence of PCP and its metabolites in brain and high degree of binding with melanin, implying a possible localisation in neuromelanin-rich substantia nigra of midbrain and locus coeruleus of pons may help explain the prolonged duration of clinical effects and persistent neurological and cognitive dysfunction several days after PCP administration.