Amphetamine Toxicity Research Articles

Integrin

Pharmacology - Oxypertine (Integrin-Bayer) has structural affinities with some major phenothiazines, such as trifluoperazine, and also with tryptophan, which has been claimed to elevate mood and increase social contacts in chronic schizophrenics.1 In animals oxypertine is a potent central depressant;2 3 it lowers body temperature, and protects mice grouped together against amphetamine toxicity, about as much as does chlorpromazine.3

D-amphetamine levels in brain and other tissues of isolated and aggregated mice

The relative tissue distribution of d-amphetamine in the mouse after i.p. administration was: kidney > lung > liver, spleen, brain > heart > blood. Aggregation of mice, which enhances amphetamine toxicity, increased amphetamine levels in blood, heart, brain, and liver, but not in other tissues. This effect occurred at a dose of amphetamine near the LD 50 dose in the aggregated mice. Aggregation also increased brain levels and toxicity of dl-4-chloroamphetamine. Chlorpromazine pretreatment prevented aggregation-induced increases in amphetamine levels in heart and brain. The possible role of increased tissue levels in the altered pharmacological effects of amphetamine produced by aggregation is discussed.

The effect of reserpine on amphetamine toxicity in aggregated mice

The effect of reserpine on amphetamine toxicity in aggregated mice

Amphetamine toxicity in hyperthyroid mice: Effects on blood glucose and liver glycogen

The effects of amphetamine and certain related drugs on mortality, blood glucose, and liver glycogen levels were compared in hyperthyroid and in euthyroid mice. Pretreatment with triiodothyronine markedly increased the mortality of mice injected with amphetamine, α-methyl- m-tyrosine, and ephedrine. In hyperthyroid but not in euthyroid mice these agents induced marked hypoglycemia and depletion of liver glycogen stores. When tested under aggregated conditions, amphetamine caused similar effects on mortality, blood glucose, and liver glycogen stores in hypothyroid and euthyroid mice. The mechanisms by which thyroid hormones influence the toxicity of amphetamine and related drugs are discussed in the light of these findings.

The effects of amine depleting agents on the toxicity of amphetamine in aggregated mice

Four hour-pretreatment with reserpine, alpha-methyl-meta-tyrosine, metaraminol or alpha-methyl-tyrosine reduced the lethality of d- amphetamine in aggregated mice. When administered simultaneously with 20 mg/kg of d- amphetamine , only alpha-methyl-tyrosine afforded protection. The amine depleting agents tested which act by releasing catecholamines, when administered simultaneously with a low dose of d- amphetamine enhanced its toxicity. Cattecholamine release in monoamine oxidase inhibited-aggregated mice produced excitement but only minimal lethality. The results of this study indicate that the release of catecholamines, and an intrinsic activity of d- amphetamine may both play a role in the enhancement of d- amphetamine toxicity by aggregation.

Effect of tranquilizing drugs on postnatal behavior

Chlorpromazine 6 mg/kg and reserpine 0.1 mg/kg were given subcutaneously to pregnant albino rats on days 4–7 of gestation in order to investigate in more detail previous reports of long-term behavioral modification of offspring by these drugs. Reserpine did not cause significant differences from controls. Chlorpromazine was shown to decrease motor activity and increase audiogenic seizure susceptibility in offspring. Those animals below average in weight and in motor activity were most likely to exhibit convulsive responses. These associated factors are interpreted as representing an altered behavioral complex. These abnormal responses were found in some animals of every chlorpromazine litter. No histological differences in the brains and no differences in susceptibility to amphetamine toxicity could be demonstrated in offspring of chlorpromazine-treated mothers.

Amphetamine toxicity in hyperthyroid mice: Effects on endogenous catecholamines

The actions of d-amphetamine were studied in mice made hyperthyroid by daily injections of triiodothyronine. The LD 50 of d-amphetamine in hyperthyroid mice was approximately one twentieth of that in euthyroid animals. d-Amphetamine induced a dose-dependent reduction of norepinephrine stores in the brain, heart, and spleen of euthyroid mice. The d-amphetamine-induced depletion of norepinephrine was significantly greater in the brain and spleen of hyperthyroid mice. d-Amphetamine had no effect on the catecholamine content of adrenal gland of hyperthyroid mice. Chlorpromazine, phenoxybenzamine, and propranolol pretreatment reduced the lethality of d-amphetamine in hyperthyroid mice while α-methyl- m-tyrosine, α-methyl- p-tyrosine, and reserpine pretreatment did not. The toxicity of α-methyl- m-tyrosine was enhanced in hyperthyroid mice. The role of endogenous catecholamines in the enhanced toxicity of d-amphetamine and α-methyl- m-tyrosine in hyperthyroid animals is discussed in the light of these findings.

The effects of alpha and beta adrenergic blockade on the lethality of amphetamine in aggregated mice

The toxicity of d -amphetamine in aggregated mice was antagonized by the alpha adrenergic blocking drugs, phenoxybezamine, tolazoline, and AHR-330. Beta adrenergic blockage produced by MJ-1999 also antagonized d -amphetamine toxicity, while toxicity was enhanced by DCI. Nethalide afforded only minimal protection and bilateral adrenalectomy was without effect.

AMPHETAMINE TOXICITY IN AGGRESSIVE MICE.

AMPHETAMINE TOXICITY IN AGGRESSIVE MICE.

Interactions between central cholinergic agents and amphetamine in mice.

Central cholinergic blockade produced by the administration of scopolamine hydrobromide significantly increased the toxicity of amphetamine in aggregated mice. Stimulation of the central cholinergic system by Tremorine, on the other hand, afforded protection against the lethal effect of amphetamine in aggregated mice, reduced spontaneous motor activity, and antagonized the effect of amphetamine on motor activity.

Antiparkinson Drugs and Neuroleptics

This chapter presents an experiment to show an antagonistic interaction between antiparkinson drugs and neuroleptics. Antiparkinson drugs inhibited the cataleptic reactions induced by the relatively high doses of phenothiazine derivatives. Antagonistic effects between the two groups of drugs were observed also concerning the spontaneous motility of mice, the avoidance behavior of rats, the group toxicity of amphetamine in mice, and the apomorphine effects in rodents, though the antagonistic interaction on these tests appeared to be dose-dependent. It seems possible to conclude that in the presence of anticholinergic agents, the increased doses of phenothiazine derivatives are required to achieve a neuroleptic effect. In contrast, some nonspecific actions of tranquillizing agents, such as drug-induced hypothermia and the effects on the “test de traction,” were not reduced by the antiparkinson drugs tested. The evidence of antagonistic effects in various tests of central activity between some phenothiazine derivatives, which may be regarded as adrenergic blocking agents, and anticholinergic drugs supports the theoretical postulation of a central antagonism between adrenergic and cholinergic mediators. The hypothesis can also be advanced that drug effects on behavior are related to central autonomic changes. Experimental studies concerning behavioral alterations induced by central cholinolytic drugs refer mostly to scopolamine and atropine, but it is likely that the synthetic compounds in clinical use as antiparkinson agents differ only quantitatively. From the results obtained in various behavioral situations, it could be assumed that anticholinergic compounds cause a disruption of normal behavior by blocking inhibitory processes. The amnesic properties of scopolamine and atropine is discussed in the chapter.

MECHANISM OF ACTION OF MONOAMINE OXIDASE INHIBITORS IN ENHANCING AMPHETAMINE TOXICITY.

MECHANISM OF ACTION OF MONOAMINE OXIDASE INHIBITORS IN ENHANCING AMPHETAMINE TOXICITY.

Drug-Induced Hyperthermia and Amphetamine Toxicity

Experiments were conducted to determine the relative importance of hyperthermia as a factor influencing the toxicity of amphetamine in aggregated and isolated mice. The ability of several agents to interfere with the hyperthermic response to amphetamine was compared with their ability to alter the incidence of lethality to this drug. It was evident that there was no direct relationship between the ability of the selected drugs to prevent the body temperature of mice from reaching the maximum temperature level of amphetamine-treated controls and their ability to protect mice from amphetamine-induced lethality. It was concluded that hyperthermia does not, in itself, appear to be the causative factor for the increased incidence of mortality to amphetamine observed in aggregated versus isolated mice.

Biochemical mechanism of amphetamine toxicity in isolated and aggregated mice

Biochemical mechanism of amphetamine toxicity in isolated and aggregated mice

EFFECT OF SENSORY STIMULI ON AMPHETAMINE TOXICITY IN AGGREGATED MICE.

THE increased toxicity of amphetamine in aggregated mice has been reported by several workers1–3. Among the factors which have been found to contribute to the enhancement of toxicity in aggregated mice are cage floor area, environmental temperature, and body-weight2–4. The present investigation has examined the effect of type of sensory contact between mice as a factor influencing amphetamine toxicity.

AMPHETAMINE TOXICITY, POPULATION DENSITY, AND BEHAVIOR: A REVIEW.

AMPHETAMINE TOXICITY, POPULATION DENSITY, AND BEHAVIOR: A REVIEW.

FATAL AMPHETAMINE POISONING.

During recent years a widespread and increasing use of the amphetamine group of drugs has been of sufficient magnitude to warrant governmental concern.¹This group of drugs including amphetamine sulfate, dextro amphetamine sulfate, and methamphetamine hydrochloride has been used for a wide variety of reasons but mainly as anorectic agents, antidepressant drugs, and routine stimulants. Although they have been generously prescribed by the medical profession, an increasingly large supply is being made available to the public through nonprofessional sources.²The general belief is that they are relatively innocuous drugs although numerous cases of amphetamine toxicity manifested by psychotic behavior have been described.^3-7Less frequently, reports have indicated that severe systemic responses^8,9primarily of sympathetic hyperactivity occur independently or accompany the more serious central nervous system disturbances of coma and convulsions.^9-11However, their potentially fatal toxic effects have been largely ignored. An extensive review of the medical literature of the

The effect of α-methyl-3,4-dihydroxyphenylalanine (methyl-dopa) and α-methyl-meta-tyrosine (α-MMT) on amphetamine toxicity

The effect of α-methyl-3,4-dihydroxyphenylalanine (methyl-dopa) and α-methyl-meta-tyrosine (α-MMT) on amphetamine toxicity

Prior Social Experience and Amphetamine Toxicity in Mice

Prior Social Experience and Amphetamine Toxicity in Mice

Hyperpyrexia as a contributory factor in the toxicity of amphetamine to aggregated mice.

A rise of body temperature into a range lethal to mice preceded death in groups of mice injected with amphetamine sulphate. At dose levels from 8.8 to 66.7 mg/kg, mortality was associated with the extent of rise in body temperature of the mice, irrespective of the actual dose administered. Isolated mice given comparable doses of amphetamine also showed a marked increase in body temperature. However, except in a very few cases, it did not rise into the range found to be lethal. Amphetamine was more toxic to isolated mice subjected to foot-shock than to isolated mice housed under normal conditions. This has also been shown to be related to the extent of rise in body temperature of the mice. The effect of a number of substances on grouped amphetamine toxicity was investigated. Chlorpromazine and phenoxybenzamine partially antagonized the sharp rise in temperature following the administration of amphetamine, and also significantly reduced mortality. Calcium acetylsalicylate was without effect on the rise of body temperature or on mortality. Both the hypothermic compound 4-methyl-5-(beta-chlorethyl)-thiazole (S.C.T.Z.) and L-thyroxine sodium potentiated the rise in temperature and caused a significant increase in mortality.