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These studies characterized the concentration-time profile of (+)-methamphetamine [(+)-METH] and its metabolite (+)-amphetamine [(+)-AMP] in the brain and five other tissues after (+)-METH administration. Male Sprague-Dawley rats received a pharmacologically active (+)-METH i.v. bolus dose (1.0 mg/kg) or a nonpharmacologically active s.c. infusion (20 h at(More)
These studies determined how high-affinity monoclonal antiphencyclidine (PCP) antigen binding fragments of immunoglobulin G (Fab) affects PCP tissue concentrations and serum protein binding in male rats. Animals received an i.v. bolus dose of 1.0 mg/kg of PCP, followed at 2 hr when distribution was complete (but about 70% of the dose remained) by either(More)
These studies examined the hypothesis that a single large dose of monoclonal anti-phencyclidine (PCP) antibody could provide long-term reductions in brain PCP concentrations despite continuous PCP administration. PCP (18 mg/kg/day, s.c.) was infused to steady-state (24 h) and then a mole-equivalent dose of a short-acting anti-PCP antigen-binding fragment(More)
RATIONALE Early environment can shape the development and function of the mesocorticolimbic dopamine (DA) system and represents a possible risk factor for adult pathologies. One critical variable in the early environment is nutrition, and exposure to high fat (HF) in adulthood is known to change this DA system. OBJECTIVES We tested whether perinatal HF(More)
Antibody therapy (as either active or passive immunization) is designed primarily to prevent drugs of abuse from entering the central nervous system (CNS). Antidrug antibodies reduce rush, euphoria, and drug distribution to the brain at doses that exceed the apparent binding capacity of the antibody. This is accomplished through a pharmacokinetic(More)
The purpose of these studies was to better understand the behavioral effects and pharmacokinetics of an i.v. bolus dose of (+)-methamphetamine [(+)-METH] in a rat model of (+)-METH abuse. We characterized the behavioral effects after increasing (+)-METH doses (0.1, 0.3, and 1.0 mg/kg) and the pharmacokinetics of (+)-METH (and its metabolite (+)-amphetamine(More)
The purpose of these studies was to explore the use of phencyclidine (PCP)-specific high affinity antibodies as a possible treatment for phencyclidine toxicity. High affinity (Kd = 1.8 nM) anti-PCP monoclonal Fab fragments were purified from papain digested anti-PCP immunoglobulin produced in mouse ascites. Control animals (n = 5) received an i.v. bolus(More)
Treatment of drug toxicity is problematic for compounds like phencyclidine (PCP) which have no known antagonists. With the advent of technology for production of large amounts of monoclonal antibody, it is now possible to explore the use of these antibodies as high affinity in vivo antagonists for treatment of PCP overdose. In the current study, the(More)
Antiphencyclidine monoclonal antibody binding fragments (anti-PCP Fab) were studied in rats as a possible treatment for phencyclidine (PCP) overdose. Each male Sprague-Dawley rat (n = 4 per group) received an i.v. dose of 1 mg/kg of PCP followed 5 min later (as toxicity maximized) by one of three treatments in a random cross-over design. The treatments were(More)
The goal of these studies was to examine the relationship between the rate of phencyclidine (PCP) administration and PCP tissue distribution. The time course of PCP distribution in serum, brain, and testis after rapid (i.v.) and slow (s.c.) administration was studied. Brain and serum PCP concentrations after an i.v. bolus dose (1 mg/kg at 900 microg/min)(More)