Amphetamine Concentrations Research Articles

Postmortem Tissue Methamphetamine Concentrations Following Selegiline Administration

Selegiline is a relatively new antiparkinson's drug whose metabolites include methamphetamine and amphetamine. A 72-year-old female with apparently suicidal intentions was found dead at her residence. The cause of death was listed as coronary heart disease with a history of polypharmacy. The tissue methamphetamine and amphetamine concentrations resulting from selegiline administration are presented in this report.

Effects of paraventricular hypothalamic microinjections of phenylpropanolamine and d-amphetamine on mash intake in rats

The present experiment compared the effects of unilateral microinjections (40, 80 and 160 nmol/0.5 μl) of phenylpropanolamine (PPA: d,1-norephedrine) and d-amphetamine sulfate within the paraventricular hypothalamus (PVN) on consumption of a palatable sweetened-mash diet in 15-hour food-deprived adult male rats. Intracranial microinjections were administered 5 minutes prior to each 30-minute feeding trial. PPA, at a dose of 160 nmol, suppressed feeding by 42%, whereas a similar dose of amphetamine suppressed feeding by 49%. Amphetamine or PPA doses of 40 and 80 nmol were without significant effect on feeding behavior. A relatively high dose of 160 nmol amphetamine was required to suppress feeding after injection into the PVN whereas much lower amphetamine concentrations are required to suppress feeding after injection into the perifornical hypothalamus. In contrast, PPA has some anorexic activity within the PVN but not within the perifornical hypothalamus.

A three-year prospective study of rearrests for driving under influence of alcohol or drugs

Fifty drunken drivers and 50 drivers with high blood drug concentrations arrested during the first four months of 1983 were selected for a study of rearrests for driving under influence of alcohol or drugs. Of the drugged drivers selected, 32 had been driving with high blood concentrations of diazepam (>1.0 μM). 50% of these drivers were rearrested during the subsequent three years. The rearrest rate was low (6%) among those who had been driving with high blood concentrations of amphetamine (>2.0 μM) or THC (>0.010 μM). Among the drunken drivers arrested (BAC >0.05%), the rearrest rate was 20%. The drivers were mostly rearrested for driving under the influence of alcohol.

Endogenous dopamine functionally activates D-1 and D-2 receptors in striatum.

Rat striatal slices incubated with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine at 1 mM were exposed to different concentrations (1-100 microM) of the catecholamine-releasing drug amphetamine. This produced both a concentration-dependent release of endogenous dopamine and accumulation of cyclic AMP in the slices. The cyclic AMP accumulation due to amphetamine was greatly increased when slices were coincubated with the selective dopamine D-2 antagonist (-)-sulpiride (30 microM), but the amphetamine-induced release of dopamine from the slices was the same in the presence or absence of (-)-sulpiride. Pretreatment of animals with reserpine (5 mg/kg s.c., 18 h before death) and in vitro incubation with alpha-methyl-p-tyrosine (50 microM for 90 min), respectively, reduced the ability of amphetamine (1-100 microM) [in the presence of 30 microM (-)-sulpiride] to induce release of dopamine and to elevate cyclic AMP accumulation in striatal slices. A similar reduction in amphetamine-induced dopamine release and cyclic AMP accumulation in striatal slices was observed 7 days following unilateral 6-OHDA lesions of the medial forebrain bundle of rats. These results suggest that amphetamine induces release of endogenous dopamine from the terminals of nigrostriatal dopamine neurones. Released dopamine is then able functionally and concomitantly to activate D-1 and D-2 receptors, seen as stimulation and inhibition of cyclic AMP accumulation, respectively.

Effects of quinidine and cimetidine on the methamphetamine level in the rat brain.

The drug interaction between methamphetamine and quinidine/cimetidine was investigated in terms of distribution of methamphetamine to the brain. The concentrations of methamphetamine and amphetamine in the brain after an s.c. injection of methamphetamine were determined in rats pretreated with a single oral dose of quinidine or cimetidine. Both drugs markedly enhanced the increase in the concentrations of methamphetamine and its metabolite, amphetamine. These results suggest that the recent finding of the enhancements of the behavioral effect of methamphetamine by quinidine and cimetidine is due to the increase in levels of methamphetamine and amphetamine in the brain by these pretreatment drugs.

Effect of ascorbic acid on brain amphetamine concentrations in the rat

1. 1. Ascorbic acid is reported to have antiamphetamine effects in rodents. 2. 2. The effect of ascorbic acid (1 g/kg ip) on the half-life of amphetamine (10 mg/kg) in rat brain using 3H-amphetamine and on amphetamine—induced stereotyped behaviour was investigated. 3. 3. Ascorbic acid had no effect on amphetamine—induced stereotyped behaviour or on the half-life of amphetamine in brain. 4. 4. If ascorbic acid antagonizes amphetamine-induced behavioural responses this is unlikely to be a result of altering the pharmacokinetics of amphetamine.

Comparison of two methods of administration of amphetamine on the dynamics of dopaminergic neurons in the rat

Dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in brain were examined in the striatum and nucleus accumbens septi after the administration of amphetamine by two different methods. A computer-controlled device was constructed to deliver intravenous injections of amphetamine in patterns mimicking those of animals in a self-administration paradigm, i.e. a total of 65 injections of 0.125 mg/kg/injection over 8 hr [total; 8.13 mg/kg (22.05 μmoles/kg)]. The second method was the intraperitoneal injection of 8.13 mg/kg as a single bolus. Control animals were intravenously or intraperitoneally administered saline. The effects of the two injection methods on the concentrations of DA and DOPAC were quite distinct at early times. This may in part be due to differences in the peak concentrations of amphetamine in brain achieved by the two regimens. Differences still persisted 48 hr after injection, particularly in the striatum. Increased levels of DA and DOPAC were observed at this time after the computer-controlled injections, while significantly decreased DA in the striatum is found after intraperitoneal bolus injections. These data strongly suggest that the method of administration of amphetamine can substantially alter the effects and possible toxicity of the drug on dopaminergic systems.

Detection of methamphetamine and amphetamine in a skeletonized body buried for 5 years

A 28-year-old male methamphetamine abuser, who had been buried for 5 years after being killed by strangulation, was found skeletonized. Methamphetamine and amphetamine in the significantly denatured fatty material of the bone marrow were analyzed by gas chromatography and gas chromatography-mass spectrometry. The confirmation of the chemicals was carried out by chemical ionization (CI) mass chromatography, CI mass spectrometry and CI mass fragmentography. The concentrations of methamphetamine and amphetamine determined by CI mass fragmentography were 1.0 μmol/100 g and 0.1 μmol/100 g, respectively. The method used would seem to be very useful for determination of methamphetamine and amphetamine in marked putrefied biological materials.

Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain

N-(2-Cyanoethyl)amphetamine (fenproporex, CE-AM) is a clinically used anorexiant claimed to be devoid of the stimulant properties associated with amphetamine (AM). This claim was inconsistent with preliminary studies conducted in our laboratories which indicated that CE-AM is metabolically dealkylated to AM to a considerable extent in the rat. Concentration-time profiles of CE-AM and its metabolites AM and 4-hydroxyamphetamine (4-OH-AM) in the rat brain were constructed after administration of CE-AM. Analyses of CE-AM, AM, and 4-OH-AM were performed by gas chromatography with electron-capture detection using pentafluorobenzoyl chloride (under aqueous conditions) as the derivatizing reagent. The half-life (t1/2) and the maximum concentration (Cmax) of AM after administration of CE-AM were calculated to be 2.04 and 0.56 times the respective t1/2 and Cmax obtained after an equimolar dose of AM. Significant differences in the profiles of 4-OH-AM were also observed. The Cmax of 4-OH-AM in rat brain after administration of CE-AM was nearly 4 times higher and the tmax (time at which concentration is maximum) 4 times lower than the respective Cmax and tmax values of 4-OH-AM observed after an equimolar dose of AM.

Studies on the mechanism of tolerance to methamphetamine

We have reported that the ability of high doses of methamphetamine to impair dopamine and serotonin synthesis in the rat brain is attenuated when animals are pretreated with gradually increasing doses of methamphetamine. To examine the mechanism of this tolerance phenomenon, the effect of methamphetamine on several neurochemical parameters was determined in naive and methamphetamine-pretreated rats. The elevation of nigral substance P concentrations by methamphetamine was attenuated in pretreated compared to naive rats. The methamphetamine-induced reduction in [3H]sulpiride binding in the rat neostriatum and nucleus accumbens was similarly attenuated in animals pretreated with methamphetamine. Determination of brain concentrations of methamphetamine and amphetamine revealed significantly lower concentrations of both compounds in the brains of pretreated compared to naive animals. The results indicate a reduction in the ability of methamphetamine to increase dopamine transmission in the brains of methamphetamine-pretreated rats. Furthermore, this effect appears to be due, at least in part, to a change in the disposition of methamphetamine in pretreated animals.

Human brain monoamine oxidase type B: mechanism of deamination as probed by steady-state methods.

Recently, evidence has been published which suggests that [Husain, M., Edmondson, D. E., & Singer, T.P. (1982) Biochemistry 21, 595-600] monoamine oxidase [amine:oxygen oxidoreductase (MAO), EC 1.4.3.4] deaminates phenylethylamine and benzylamine via two distinct kinetic pathways which involve either binary or ternary complex formation, respectively. These conclusions were drawn largely from stopped-flow kinetic analysis performed on purified enzyme removed from its native membrane and in the presence of the inhibitory detergent Triton X-100. In this study, d-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme. Initial velocity studies showed mixed-type patterns for amphetamine inhibition of phenylethylamine, tryptamine, and tyramine when either amine or oxygen was the varied substrate. Slope and intercept vs. amphetamine concentration replots were linear in all cases except for phenylethylamine (hyperbolic); Ki values obtained from linear replots of slope or intercept values were comparable. In contrast, amphetamine was a competitive inhibitor of benzylamine deamination when amine concentration was varied and uncompetitive when oxygen concentration was varied; slope and intercept replots were linear for both. When benzylamine was the alternative substrate inhibitor and tyramine and tryptamine deamination was measured, mixed-type inhibition patterns were obtained when either amine or oxygen concentration was varied; replots of slope and intercept were linear in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of amphetamine, cocaine, and heroin vapour pressures using a dynamic gas blending system and gas chromatographic analysis

A dynamic gas blending system was used to generate controlled vapour concentrations of amphetamine, cocaine, or heroin. An adsorption – thermal desorption – gas chromatographic procedure was developed and used to measure the output vapour concentrations. The vapour pressure of amphetamine at 20 °C was determined, and vapour pressures as a function of temperature have been measured for cocaine and heroin.

Amphetamine secretion in breast milk

The excretion of amphetamine in human breast milk was studied in a nursing mother with narcolepsy, who was treated with 20 mg daily of a racemic preparation of amphetamine. The concentration of amphetamine was 3 and 7 times higher in breast milk than in maternal plasma on the 10th and 42nd days after delivery. Small amounts of amphetamine were found in urine samples from the infant.

Effects of antipsychotic drugs on the long-term effects of amphetamine on nigro-striatal dopamine neurons in iprindole-treated rats.

The decrease in striatal dopamine (DA) at 1 week after the administration of a single injection of (+)-amphetamine sulfate (9.2 mg/kg) to iprindole-treated (10 mg/kg of iprindole hydrochloride) rats was prevented by haloperidol (0.2 mg/kg), sulpiride (32 mg/kg), pimozide (2 mg/kg), chlorpromazine hydrochloride (3.5 mg/kg), fluphenazine 2-hydrochloride (0.25 mg/kg) and (+)-butaclamol hydrochloride (1 mg/kg) but not by (-)-butaclamol hydrochloride (1 mg/kg) or clozapine (40 mg/kg). The same dose of sulpiride did not significantly attenuate the rotational behavior induced by the administration of (+)-amphetamine sulfate (9.2 mg/kg) to iprindole-treated rats with unilateral aspiration lesions of the striatum. The concentration of amphetamine in the brains of iprindole-treated rats at 8 h after (+)-amphetamine sulfate (9.2 mg/kg) administration was not altered by the coadministration of haloperidol (1 mg/kg), sulpiride (32 mg/kg), pimozide (2 mg/kg) or clozapine (40 mg/kg). Recovery of striatal DA after depletion by alpha-methyl-m-tyrosine (alpha MMT) (50 mg/kg) was facilitated by haloperidol (0.2 mg/kg) and sulpiride (32 mg/kg) but not by clozapine (40 mg/kg). The possibility that neuroleptic drugs antagonize both the short-term depletion of striatal DA produced by alpha MMT and the long-term depletion of striatal DA produced by amphetamine in iprindole-treated rats by an effect on the nerve impulse-mediated release of vesicular transmitter is discussed.

Intersex difference in striatal amphetamine concentration is independent of age

Amphetamine sulfate (1.0 mg/kg) was administered intraperitoneally to two groups of male and female rats, 5 and 15 weeks of age. After 30 minutes, striata were removed and analyzed for amphetamine concentrations using gas-liquid chromatography. Females were found to have significantly higher levels of amphetamine regardless of age. These results indicate that mechanisms other than drug disposition are responsible for the previously reported behavioral sex differences that occur after administration of amphetamine.

Amphetamine-stimulated release of endogenous dopamine from the rat caudate nucleus in vivo.

The in vivo release of endogenous dopamine (DA) has been measured from the rat caudate nucleus. A push-pull cannula was implanted into the brain and the tissue was perfused with artificial cerebrospinal fluid (CSF) containing amphetamine in concentrations ranging from 5 X 10(-3) to 5 X 10(-7) M. The DA released into the perfusate was determined by a radioenzymatic procedure. DA release was increased to levels significantly above its resting rate by amphetamine concentrations of 5 X 10(-6) M or greater. Release stimulated by 5 X 10(-5) M amphetamine was significantly reduced by removing calcium from the perfusing fluid; the unstimulated release rate was not significantly affected. The concentrations of amphetamine required to increase DA release in vivo would appear to be similar to those found in the brain following intraperitoneal doses which produce increases in locomotor activity and stereotyped behavior.

CI-mass fragmentographic analysis of methamphetamine and amphetamine in human autopsy tissues after acute methamphetamine poisoning

A 22-year-old male methamphetamine abuser was put under police protection owing to his abnormal state of excitation, but died 1 h later. Distribution of methamphetamine and amphetamine in the body was analyzed by the chemical ionization mass fragmentographic method. Amphetamine/methamphetamine concentrations (μmol/100 g) were 0.24 5.59 in blood, 0.41 9.43 in liver, 0.41 10.02 in brain, 0.37 9.80 in kidney, 0.18 4.57 in muscle, 0.02 0.63 in subcutaneous fat and 1.87 1464 in gastric contents. Total amount of methamphetamine hydrochloride in stomach contents was about 54 mg. Amphetamine concentrations in tissues ranged from 3.2% to 4.3% of methamphetamine, and was 0.1% in stomach contents. Amphetamine in tissues seems to be a metabolite of methamphetamine, and amphetamine in gastric contents is presumed to result from gastric mucous excretion. The blood concentration of methamphetamine was at a fatal level, and the total amount of the drug in gastric contents indicates that fatal poisoning occurred by ingestion.

Propylhexedrine-induced left ventricular dysfunction.

Brief Reports1 October 1982Propylhexedrine-Induced Left Ventricular DysfunctionCHARLES H. CROFT, M.D., BRIAN G. FIRTH, M.D.; D. Phil., L. DAVID HILLIS, M.D.CHARLES H. CROFT, M.D.Search for more papers by this author, BRIAN G. FIRTH, M.D.; D. Phil.Search for more papers by this author, L. DAVID HILLIS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-4-560 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAmphetamine abuse has previously been implicated in the pathogenesis of congenital heart disease (1), necrotizing vasculitis (2), intracranial hemorrhage (3), pulmonary fibrosis, and cor pulmonale (4). Although animal studies have shown a relation between myocardial amphetamine concentrations and toxicity (5), only one patient has been described in whom the chronic use of oral dextroamphetamine was associated with a cardiomyopathy (6). We describe four patients with severe left ventricular dysfunction in association with chronic abuse of the amphetamine analog, propylhexedrine.Between September 1978 and February 1982, four men who were chronic abusers of intravenous propylhexedrine (Benzedrex, Smith Kline & French Laboratories,...

The Application of Derivative UV-Visible Spectroscopy in Forensic Toxicology

A preliminary study on the applications of UV-visible derivative spectroscopy to forensic toxicology has been conducted. The presentation of data in the derivative mode has considerable potential as an aid to the identification of compounds with very similar UV-visible spectra. The value of second-derivative spectra for the elimination of broad background absorbance is demonstrated using a liver extract containing a low concentration of amphetamine. Two commercial UV-visible spectrometers have been used which employ different methods of obtaining derivative spectra (electronic differentiation and numeric differentiation) and the limitations due to wavelength shifts produced by the former are discussed.

Comparison of the release of [ 3h]dopamine from isolated corpus striatum by amphetamine, fenfluramine and unlabelled dopamine

Amphetamine-induced release of previously accumulated [ 3H]dopamine ([ 3H]DA) was compared to the release of [ 3H]]DA produced by unlabelled DA and fenfluramine. Like unlabelled DA, amphetamine was more potent than fenfluramine in releasing [ 3H]DA in all tissue preparations (untreated, pargyline-treated, and pargyline- and reserpine-treated corpus striatal slices). In tissue treated with both reserpine and pargyline, benztropine greatly reduced the efflux of [ 3H]DA produced by amphetamine and unlabelled DA but had only a slight effect on fenfluramine-induced release of [ 3H]DA. In the same tissue preparation, Q 10 values for the release of [ 3H]DA produced by 3 × 10 −7 M amphetamine (1.8) and 3 × l0 −6M unlabelled DA (1.7) were similar to that for the spontaneous release of [ 3H]DA (1.7). However, when the concentrations of amphetamine and unlabelled DA were increased to 10 −4 M, the Q 10 values for the release of [ 3H]DA were diminished at the lower temperatures. These results suggest that amphetamine may release [ 3H]DA by two mechanisms: (1) by accelerated exchange diffusion due to its use of the DA uptake carrier to enter into neurons (this would predominate at low concentrations of amphetamine), and (2) by passive entrance into neurons and displacement of [ 3H]Da from binding sites (this would predominate at high concentrations of amphetamine).