Michael A. Peat

Long-term effects of methamphetamine on the synthesis and metabolism of 5-hydroxytryptamine in various regions of the rat brain

Abstract Repeated administration of methamphetamine for 30 hr produced large decreases in the activity of tryptophan hydroxylase and in the levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in several serotonergic nerve terminal regions of the rat brain. Six sequential doses of methamphetamine (15 mg/kg, s.c.), given every 6 hr, produced a differential regional reduction in the levels of 5-HT, 5-HIAA and in tryptophan hydroxylase activity. Among the regions tested, the neostriatum and cerebral cortex were most affected and the hypothalamus was least affected. A significant recovery in the levels of 5-HT, 5-HIAA and tryptophan hydroxylase activity had occurred by 10 days following drug treatment. Recovery of enzyme activity in the hypothalamus, spinal cord and olfactory tubercle was complete, whereas enzyme activity was still significantly depressed in the neostriatum, nucleus accumbens, cerebral cortex and hippocampus. Similar trends were obtained for 5-HT and 5-HIAA. Tryptophan levels in some regions were increased at 36 hr and remained elevated 110 days after methamphetamine treatment.

High-performance liquid chromatographic determination of indoleamines, dopamine, and norepinephrine in rat brain with fluorometric detection☆

A high-performance liquid chromatography-fluorescence procedure for the determination of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tryptophan, dopamine, and norepinephrine has been developed. The method uses an ion-pairing system on an Ultrasphere ODS (5-microns) column with detector wavelength settings of excitation at 290 nm and emission at 330 nm. The procedure has been used to quantitate these indoleamines and catecholamines in rat brain tissue after homogenization in a perchloric acid solution; an aliquot of this solution is injected directly onto the HPLC column. Column sensitivities range from 6.1 pmol for tryptophan to 1.1 pmol for 5-hydroxytryptamine.

The acute effects of methamphetamine, amphetamine and p-chloroamphetamine on the cortical serotonergic system of the rat brain: Evidence for differences in the effects of methamphetamine and amphetamine

Cortical tryptophan hydroxylase (TPH) activity was reduced 3 h after a 10 or 15 mg/kg i.p. dose of either amphetamine (AMP), methamphetamine (METH), or p-chloroamphetamine (PCA). These injections of METH or PCA also decreased cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations; none of the four doses of AMP decreased indoleamine concentrations. The time course of the effects following a 15 mg/kg dose of each amine was also different. Cortical TPH activity was reduced by all three amines for periods up to 24 h, whereas only METH and PCA significantly decreased 5-HT and 5-HIAA concentrations for long periods. These data suggest that each of the amphetamines may inhibit TPH activity, whereas only METH and PCA produced long-lasting decreases in indoleamine concentrations, reflecting either varying degrees of toxicity or differential effects of AMP on enzyme activity and neurotransmitter concentrations.

The Screening and Quantitation of Diazepam, Flurazepam, Chlordiazepoxide, and Their Metabolites in Blood and Plasma by Electron-Capture Gas Chromatography and High Pressure Liquid Chromatography

A combined GLC-ECD and HPLC procedure has been developed for the analysis of the most commonly encountered benzodiazepine drugs and has been applied to both plasma and postmortem blood samples. There is no doubt that since their introduction the use of these sensitive analytical methods have resulted in an increase in the incidence of detection of these drugs in both clinical and forensic toxicology cases.

Concentrations of Lidocaine and Monoethylglycylxylidide (MEGX) in Lidocaine Associated Deaths

Concentrations of lidocaine and MEGX were determined in a variety of tissues and other samples collected at autopsy. In 13 of the cases examined in which lidocaine was associated with death, tissue concentrations were greater than 15 mg/kg. Tissue concentrations in other patients treated with lidocaine were significantly lower.

Effect of cimetidine on verapamil disposition

The effects of multiple doses of cimetidine on single‐dose verapamil kinetics were studied in nine healthy men. Baseline hepatic blood flow was estimated by indocyanine green elimination on day 1. On day 2, the subjects received verapamil, 10 mg iv, after which the plasma concentration—time profile was determined. After a 2‐day washout, cimetidine, 300 mg, was taken by mouth four times a day for 5 days. The indocyanine green study was repeated on day 9 and verapamil was taken on day 10. Cimetidine reduced verapamil clearance by 21% and increased the elimination t½ by 50%. The volume of distribution at steady state did not change. Cimetidine increased hepatic blood flow in some subjects, while decreasing it in others. There was no correlation between individual changes in verapamil clearance and hepatic blood flow. These data indicate that cimetidine reduces verapamil clearance by mechanism(s) other than a change in hepatic blood flow or volume of distribution.

Profiles of delta 9-tetrahydrocannabinol metabolites in urine of marijuana users: preliminary observations by high performance liquid chromatography-radioimmunoassay.

Metabolic profiles of 11-nor-9-carboxylic acid-delta 9-tetrahydrocannabinol (COOH-THC) and other THC metabolites were determined in an infrequent and a frequent marijuana user by high performance liquid chromatography-radioimmunoassay (HPLC-RIA). In the infrequent user, no unconjugated COOH-THC was detected in urine samples for the first 8 h following smoking, whereas this metabolite was detected in the urine samples from a frequent user. A metabolite was also detected in the frequent user, which was not present in the urine sample from the infrequent user.

Drugs and driving: a systematic analytical approach

To collect useful epidemiological data about drug involvement in highway safety, it is essential that sensitive and specific analytical procedures be used to establish the presence of and to determine the concentrations of drugs and metabolites in samples collected from drivers. This paper describes a comprehensive and systematic screening procedure requiring 6 mL of blood, which has been used for the analysis of samples collected from injured and fatally injured drivers. The procedure uses radioimmunoassay, gas chromatography with selective detectors, and high performance liquid chromatography. Drugs and metabolites presumptively identified are then confirmed primarily using gas chromatography--chemical ionization mass spectrometry.

Toxicological findings in a fatal overdose of verapamil.

Presented is a case where the death was attributed to the deliberate ingestion of an overdose of verapamil (V). Blood, urine, and gastric concentrations of the drug were determined by gas chromatography with nitrogen phosphorus detection (GC-NPD). Identification of norverapamil (NV) was made. A presumptive identification of o-demethylnorverapamil (DNV) was also made.

High Performance Liquid Chromatography-Immunoassay of Δ9-Tetrahydrocannabinol and Its Metabolites in Urine

High performance liquid chromatographic-immunoassay (HPLC-IA) profiles of cannabinoid metabolites in urine samples were obtained using four different antisera. The urines were chromatographed on a reverse phase system using a gradient of acetonitrile in water (pH 3.3) and fractions collected every 30 s. Some urine samples were hydrolyzed with methanolic sodium hydroxide before fractionation. Peaks of immunoreactivity were detected at a fraction corresponding to 11-nor-9-carboxy-delta 9-tetrahydrocannabinol (COOH-THC) and at an early eluting fraction; however, the profiles depended upon the specificity of the antisera used.