Postmortem release of amitriptyline from the lungs; a mechanism of postmortem drug redistribution.

An experimental rat model was used to study postmortem redistribution of amitriptyline (AMI). Two hours after a subcutaneous injection with 20 mg of amitriptyline, the rats (n = 40) were anaesthetized and blood samples were drawn from the femoral vein and the heart. The rats were then sacrificed by CO2 and left at room temperature for either 0.

Relationship between unbound plasma concentrations and various psychomotor and subjective effects after intakes of diazepam and flunitrazepam.

Unbound plasma concentrations of diazepam and flunitrazepam were related to psychomotor and subjective effects of the two drugs. The interindividual variability in plasma protein binding of both diazepam (98.5 +/- 0.

Morphine-6-glucuronide: a potent stimulator of locomotor activity in mice.

The present study tested the hypothesis that morphine glucuronides have stimulant properties by studying their effects on locomotor activity in mice. Drug-naive C57BL/6J male mice were injected with saline, morphine, morphine-6-glucuronide (M6G) or morphine-3-glucuronide (M3G). In some experiments, mice were injected with saline or naloxone 5 min prior to drug treatment.

Development of acute tolerance after oral doses of diazepam and flunitrazepam.

Flunitrazepam (1 and 2 mg), diazepam (10 and 20 mg) or placebo was administered to healthy, male volunteers, and the time course of psychomotor impairment, as indicated by simple and complex choice reaction time and movement time, was studied during a period of 6 h after drug intake. To examine whether acute tolerance developed, the observed performance during decreasing drug plasma concentration was compared to the predicted performance based on kinetic-dynamic modelling of the observed performance during the first 1.5 h after intake when the drug plasma concentrations were increasing or at peak level.

Different biotransformation of morphine in isolated liver cells from guinea pig and rat.

The biotransformation of morphine was characterized in freshly isolated parenchymal and non-parenchymal liver cells from rats and guinea pigs in suspension culture to establish an in vitro model for morphine metabolism. Liver cells were prepared by a collagenase perfusion technique, and separated by differential centrifugation. Morphine metabolism was investigated at different concentrations (1, 5, 100 and 200 microM).

Incidence of alcohol and drugs in fatally injured car drivers in Norway.

Blood samples from 159 fatally injured drivers from 1989 and 1990, corresponding to 57% of all fatally injured drivers in Norway during this period, were analysed for alcohol and psychoactive drugs. Alcohol was found in 28.3% of the drivers, 27.

Ethylmorphine metabolism in isolated rat hepatocytes.

The metabolism of ethylmorphine has been studied in suspensions of isolated rat hepatocytes. Early during incubation, the two major metabolic intermediates detected were morphine and norethylmorphine following N- and O-dealkylation of ethylmorphine, respectively. During subsequent incubation the concentration of the second metabolic intermediate, normorphine increased, before the concentration peaked at approximately 20 microM (100 microM ethylmorphine).

An animal model of postmortem amitriptyline redistribution.

An experimental rat model was developed to study postmortem changes of drug concentration after an acute overdose. Overnight fasted rats were fed 75 mg of amitriptyline (AMI). Two h after dosing, the rats were anaesthetized and blood samples were drawn from the femoral vein (peripheral blood--PB) and the heart (HB).

Amnesic effects and subjective ratings during repeated dosing of flunitrazepam to healthy volunteers.

Flunitrazepam (1 mg) or placebo was administered once daily over a treatment period of 8 days to healthy, male volunteers to study the time course of the effects on memory functions and on subjective ratings of alertness and tension. The plasma level of flunitrazepam increased by approximately 40% (P < 0.05) during the treatment period.

Types of drug-testing programmes in the workplace.

The article begins with a discussion of the common features of drug-testing programmes. Regulations, procedures and methods for the collection of biological specimens, the subsequent handling and analysis of the specimens and the reporting of the interpreted results are all important aspects to be dealt with in testing programmes. Different types of testing are examined.

Co-variation between biological markers and self-reported alcohol consumption. A two-year study of the relationship between changes in consumption and changes in the biological markers gamma-glutamyl transpeptidase (GGT) and average volume per erythrocyte (MCV) among problem drinkers.

Co-variations between self-reported alcohol consumption and the biological markers MCV (average volume per erythrocyte) and GGT (gamma-glutamyl transpeptidase) over a 2-year period were studied in a group of 84 men and 53 women recruited to out-patient treatment by advertisements in the press. Upon admission, the drinking pattern of the participants during the preceding year was registered in detail. The participants were also medically examined, and blood samples taken.

[Neurobiological aspects of addictive drugs].

Increasing insight into the molecular and cellular mechanisms of drugs of abuse has been obtained during the last decade. Such drugs exert several of the effects related to their abuse potential by interacting with the mesocorticolimbic dopaminergic system. Single doses of several drugs of abuse increase dopamine activity in nucleus accumbens, which is related to reward and reinforcement.

Measuring ethanol in blood and breath for legal purposes: variability between laboratories and between breath-test instruments.

We determined the concentrations of ethanol in nearly simultaneous specimens of venous blood (BAC) and end-expired breath (BrAC) after healthy volunteers drank moderate amounts of alcohol. BAC was measured at two laboratories and BrAC was analyzed with two instruments (Intoxilyzer 5000) from the same manufacturer. The mean difference in BAC between laboratories was 0.

Clinical responses in relation to blood acetaldehyde levels.

A study was undertaken to examine the relationship between blood acetaldehyde levels and clinical responses in volunteers receiving the anti-alcohol drugs disulfiram and calcium cyanamide. In the first part of this study volunteers received different doses of disulfiram (125 mg and 500 + 250 mg), of calcium cyanamide (25 mg, 50 mg and 100 mg) and of ethanol (0.2 g/kg orally and 0.

Relationship between drug plasma concentrations and psychomotor performance after single doses of ethanol and benzodiazepines.

In a placebo controlled, crossover study psychomotor effects of single doses of diazepam, 10 and 20 mg, flunitrazepam, 1 and 2 mg, as well as 0.9 g ethanol/kg body weight were investigated over a time period of 6 h in 12 healthy men. Blood samples were collected simultaneously with the test sessions to determine drug concentrations in plasma or blood.

Diffusion as a mechanism of postmortem drug redistribution: an experimental study in rats.

In some cases of drug overdose there is a reservoir of unabsorbed drug in the stomach and gut. Furthermore, agonal aspiration might establish a second reservoir in the lungs. Two experimental rat models were used to study if diffusion from these reservoirs could contribute to the phenomenon of postmortem drug redistribution.

Depot preparations of disulfiram: experimental and clinical results.

Patient compliance with disulfiram is a troublesome clinical problem. Several strategies have been proposed as a solution to the problem, including subcutaneous implantation of disulfiram. However, well controlled studies of alcoholics and healthy volunteers have failed to discover a pharmacological effect of implanted disulfiram.

[Substance abuse analysis of biological materials].

Requests are increasing for biomedical analyses of abused drugs in forensic toxicology, tests at work, testing of drug addicts during rehabilitation, and in therapeutic and other situations. Special guidelines have been prepared in forensic toxicology, with regard to the legal background, information on any sanctions in the event of positive test results, chains of custody for handling samples, analytical methods with known specificity and sensitivity, and interpretation of results based on information of legal drug use. These guidelines should also be recommended in other cases if the results might lead to negative sanctions for the individuals involved.