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PubMed1987

Effects of cocaine on methamphetamine-induced neurochemical changes: characterization of cocaine as a monoamine uptake blocker.

Many of the rewarding aspects of cocaine are thought to be due to the ability of this stimulant to block reuptake of monoamines. However, because of its ability also to cause transmitter release, it is difficult to examine the properties of cocaine as an uptake blocker using in vitro techniques such as tissue slices or synaptosomes. Thus, we have evaluated cocaine as a blocker of dopamine and 5-hydroxytryptamine uptake processes by determining the in vivo effect of concurrent administrations of cocaine on the neurochemical effects of methamphetamine treatments. These findings demonstrated that cocaine like 5-hydroxytryptamine uptake blockers such as citalopram, greatly attenuated or blocked decreases in striatal and cortical tryptophan hydroxylase activities and concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid induced by multiple and single methamphetamine administrations. In contrast to other dopamine uptake blockers, such as amfonelic acid, cocaine did not attenuate the methamphetamine effects on striatal tyrosine hydroxylase activity and the concentrations of dopamine, dihydroxyphenylacetic acid and homovanillic acid. The neurochemical findings were correlated with behavioral analyses.

Animals↗

PubMedDate not supplied

Effect of L-histidine pretreatment on methamphetamine induced sterotyped behaviour in rats.

Pretreatment with L-histidine precursor of histamine was found to delay the onset, shorten the duration and decrease the intensity of stereotyped behaviour induced by methamphetamine while chlorcylizine a H1 receptor blocker was found not only to potentiate methamphetamine induced sterotyped behaviour but also to block the inhibitory effect of L-histidine on methamphetamine stereotypy. Our results indicate that the central histaminergic system by exerting a modulatory influence on the striatal dopaminergic system may influence the functioning of the extrapyramidal motor system.

Animals↗

PubMed1983

Effects of a single dose of methamphetamine and iprindole on the serotonergic and dopaminergic system of the rat brain.

A single dose (17.5 mg/kg i.p.) of methamphetamine was administered to iprindole-treated (10 mg/kg i.p.) rats. Forebrain concentrations of methamphetamine and amphetamine were significantly increased in iprindole-treated rats 1 and 6 hr after injection; in contrast to rats pretreated with saline, both amines were also detected after 18 hr. Three and 7 days after injection, significant decreases were seen in tryptophan hydroxylase (TPH) activity and serotonin concentrations in the cerebral cortex, neostriatum and hypothalamus. Hypothalamic TPH activity had recovered by 14 days. Neostriatal tyrosine hydroxylase activity and dopamine concentrations were significantly depressed at all time points examined. Iprindole alone produced a significant increase in cortical TPH activity after 1 day. After 3 days, TPH activity was significantly decreased when compared with control, whereas serotonin and 5-hydroxyindoleacetic acid concentrations were significantly increased. This study demonstrates that persistence of methamphetamine and/or amphetamine at the site of action is important for neurotoxicity.

Amphetamines↗

PubMed1981

Behavioral supersensitivity to methamphetamine following chronic treatment with (--)-sulpiride in the rat.

Hyperactivity induced by methamphetamine (4 mg/kg i.p.) was actographically evaluated in rats chronically treated with sulpiride stereoisomers and haloperidol. The trial was repeated with half dose of the stimulant after 8 days of neuroleptic withdrawal. (--)-Sulpiride and haloperidol antagonized the response to the full dose of methamphetamine and induced behavioral supersensitivity to the challenging dose. (+)-Sulpiride strongly enhanced the effect of 4 mg/kg of methamphetamine, but no relevant changes in dopaminergic sensitivity followed.

Animals↗

PubMed1981

[A metrical analysis of exploratory behavior in mice: effects of methamphetamine and diazepam (author's transl)].

Exploratory behavior can be considered a kind of positional behavior. The theory for the analysis of exploratory behavior by the presented method is based on the concept of the Markov process. The following parameters were used in this experiment; (1) frequency of visits to all the positions that are unit spaces expedient to the observation (N), (2) Entropy (HI), a measure of the spacial distribution of animal location, (3) Entropy (HII), a measure of the degree of disorder in movement direction, and (4) length of the longest path passed frequently (L), calculated by examining an upper confidence limit for a parameter of a binomial distribution. Both methamphetamine and diazepam increased N at lower doses, and increased L dose-relatedly. Methamphetamine decreased the values of HI and HII. Diazepam increased HI value while decreased HII value. These results indicate that the effect of methamphetamine on the exploratory behavior in mice is to narrow their behavior space and to make their movement pattern monotonous, back and forth within a small area (i.e. stereotyped behavior), and the effect of diazepam is to extend their behavior space and also simplify their movement pattern, going round and round over a wide area in the apparatus. The results of this experiment suggest that the present method is useful for analysis of exploratory behavior and a better understanding of the effects of psychotropic drugs.

Animals↗

PubMed1976

Absence of pathological changes following intravenous methamphetamine and intra-arterial iothalamate meglumine.

Eleven Rhesus monkeys received injections of intravenous methamphetamine hydrochloride (Desoxyn) and/or intra-arterial 60% iothalamate meglumine (Conray) according to a schedule previously reported to produce marked radiological and pathological changes in the cerebral vasculature of the Rhesus monkey. While radiological changes consistent with impaired cerebral circulation were observed, they could not be correlated directly with the administration of intravenous methamphetamine because of the trauma and variability of the technique utilized. Moreover, significant pathological changes could not be found in animals given intravenous methamphetamine alone, intra-arterial iothalamate meglumine alone, or both drugs together. This was true for both drug naive and drug experienced monkeys. These results suggest: (1) radiological changes consistent with decreased cerebral blood flow are not necessarily pathognomonic for reported morphological lesions, and (2) further investigation is required to determine the specific factors necessary to cause the previously reported changes.

Animals↗

PubMed1996

The detection of a metabolite of alpha-benzyl-N-methylphenethylamine synthesis in a mixed drug fatality involving methamphetamine.

A 37-year-old, white male collapsed at his home following a party. He reportedly had a history of unspecified cardiac arrhythmia. The ambulance crew found him unresponsive and an ECG revealed ventricular tachycardia/fibrillation. Following one hour of resuscitative efforts in the ambulance and emergency room of a local hospital, he was pronounced dead. An antemortem urine toxicology screen performed at the hospital was "positive" for benzodiazepines, cocaine and amphetamine/methamphetamine. At autopsy, there was generalized organ congestion with no evidence of trauma or other significant pathology except mild, left ventricular hypertrophy. Quantitation by gas chromatography/mass spectrometry (GC/MS) of methamphetamine in bile, blood, urine and gastric contents yielded 21.7, 0.7, 32.0 and 2.9 mg/L, respectively. Liver and brain contained 2.2 and 2.7 mg/kg, respectively. A trace amount of p-OH-alpha-benzyl-N-methylphenethylamine (p-OH-BNMPA), a metabolite of alpha-benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, was also detected in the urine. Since these impurities can be characteristic of a particular synthetic method, their presence in seized samples or their detection in biological samples from methamphetamine users can further be used to monitor the sales of precursor chemicals, group seized compounds to common sources of illicit production or provide links between manufacturers, dealers and users.

Adult↗

PubMed1996

Identification of n-acetylmethamphetamine in a sample of illicitly synthesized methamphetamine.

Analysis of illicit methamphetamine samples revealed the presence of a hitherto unreported impurity. This was identified as N-acetylmethamphetamine by synthesis and GC-MS. This impurity is believed to arise by transesterification of methamphetamine during reflux with propyl acetate. Other circumstantial evidence and intelligence data indicate that propyl acetate was used to increase yields of methamphetamine hydrochloride by azeotropic removal of water remaining after salt formation with aqueous hydrochloric acid.

Drug Contamination↗

PubMed1996

Methamphetamine and methylenedioxymethamphetamine neurotoxicity: possible mechanisms of cell destruction.

Methamphetamine and MDMA as well as similar substituted phenethylamines are toxic to DA and/or 5-HT neurons. The duration and magnitude of these effects are dose dependent and are accompanied by different degrees of recovery. MDMA-induced 5-HT damage persists for up to 52 weeks in the rat, and methamphetamine-induced DA damage persists for up to 3 years in the rhesus monkey. Several possible mechanisms of amphetamine-analog toxicity have been reviewed. The excitatory feed-forward loop theory is best supported by the literature. This theory, however, is very wide ranging and difficult to prove or disprove. The hydroxy radical and DA mediation theories are both well supported by the data reviewed. It should be noted that these two hypotheses are closely related to each other. The DA mediation theory is based on the requirement of an intact DA system for methamphetamine and MDMA neurotoxicity to occur. The hydroxy radical theory is also based on the presence of DA and 5-HT; in addition, it suggests the formation of toxic hydroxy radicals from DA or 5-HT as the specific mechanism for the amphetamine-analog neurotoxicity. The hydroxy radical theory also accounts for the fact that amphetamine-analog neurotoxicity is selectively toxic to the DA and/or 5-HT systems of the brain; that is, the toxin is formed either in the synapse or within the neurons that release DA and/or 5-HT as a result of amphetamine analog treatment. The toxic drug metabolite theory, while not exhaustively studied, has little support from the literature at present. Similarly, the NMDA receptor mediation theory, in its most straightforward form, also has little support from the literature. The protective effects of the NMDA receptor antagonist MK-801 may be a modulatory effect resulting from changes in temperature regulation, rather than a direct effect of antagonizing a link in the toxic mechanism itself. It should be noted that the effects of the protective agent plus amphetamine-analog combinations on body temperature, when thoroughly investigated, may serve to separate agents which protect through a cooling mechanism from agents that protect by interfering with the toxic process itself.

Animals↗

PubMed1996

Case report: distribution of methamphetamine in a massive fatal ingestion.

A subject who apparently swallowed a baggie containing "crank" (methamphetamine) while being arrested, was admitted to hospital and then experienced a massive overdose of the drug. The subject went through a seizure with associated fixed dilated pupils, and a depressed pulse and blood pressure. His cardiac and respiratory problems could not be stabilized, and he died. Methamphetamine levels in central and peripheral blood, liver, bile, vitreous, gastric and urine were determined. Blood levels of greater than 60 mg/L, were found together with even higher levels in the bile, urine and gastric. These levels are discussed in terms of other fatal, non-fatal and recreational methamphetamine use.

Adult↗

PubMed1997

Repeated binge exposures to amphetamine and methamphetamine: behavioral and neurochemical characterization.

Stimulant psychosis and addiction are most commonly associated with repeated, high-dose binges or runs, typically preceded by a more intermittent pattern of stimulant abuse. We previously reported that rats exposed to an escalating dose-run pattern of amphetamine administration exhibited changes in their behavioral response profile that differed both qualitatively and quantitatively from the response to either acute or intermittent daily treatment. To determine the generality of these effects and characterize further the nature of the behavioral and neurochemical changes of this treatment, rats received single daily injections of amphetamine (2.5 or 4.0 mg/kg s.c.) or equimolar doses of methamphetamine, followed by multiple runs (four daily injections at 2-hr intervals) with the pretreatment dose. This treatment resulted in a unique behavioral profile, including a profound increase in the relative expression of locomotion vs. stereotypy. The markedly enhanced poststereotypy locomotor activation was characterized by repeated "burst"-like episodes of ambulation. The number of runs required for the emergence of this behavior was dose dependent and was similar for the two drugs except that with methamphetamine, there also was a marked prolongation of the poststereotypy locomotor response during run exposures. During runs, both drugs produced a decline in the caudate but not the nucleus accumbens microdialysate dopamine response, whereas only methamphetamine produced a decline in the serotonin response that was apparent in both regions. The possible relationship between these behavioral and neurochemical changes and their implications for high dose patterns of stimulant abuse are discussed.

Amphetamine↗

PubMed1998

Methamphetamine poisoning in three Oklahoma dogs.

Methamphetamine is an amphetamine derivative and a category II controlled substance. It is uncommonly prescribed by physicians, but is more often used illegally as a stimulant. In this case study, 3 dogs were believed maliciously poisoned. Methamphetamine was detected in the stomach contents of 1 dog. One died and 2 recovered after gastrointestinal decontamination and supportive care. The recommended treatment protocol of methamphetamine toxicosis should also include urine acidification and alpha-adrenergic blocking agents.

Animals↗

PubMed1976

Detection of amphetamine and methamphetamine-type materials in pharmaceutical and biological fluids by fluorometric labeling.

A rapid and sensitive method for detecting amphetamine and methamphetamine in drug preparations and biological fluids has been developed. Amphetamine and methamphetamine in pharmaceutical and clandestine drug preparations can be easily screened from other contaminating drugs and readily identified by their fluorescence, with subsequent separation accomplished by TLC. The same general procedure can also be used to detect amphetamine and methamphetamine in human urine at concentrations of 0.1 mug/ml.

4-Chloro-7-nitrobenzofurazan↗

PubMed1998

Clinical manifestations and prognostic features of acute methamphetamine intoxication.

The prevalence of amphetamine abuse and the frequency of emergency department visits for amphetamine intoxication have increased dramatically worldwide. In this study, we retrospectively investigated the relationship between the prognostic features and clinical manifestations among patients admitted to the emergency department of a university hospital for acute methamphetamine intoxication during a 6-year period. Data collected included gender, age, route of abuse, time between drug exposure and arrival at the emergency department, estimated dose, signs and symptoms, laboratory values, and complications. Emergency therapy and cooling procedures were also recorded. After excluding 26 patients with multiple-drug intoxication, 18 patients (male-to-female ratio, 11:7) were include in the analysis. The mean age was 25.6 years. Thirteen patients survived and five died. Patients who died often presented with coma (80% vs 0%, p = 0.002), shock (60% vs 8%, p = 0.044), convulsions (100% vs 23%, p = 0.007), oliguria (80% vs 0%, p = 0.002), and high body temperature (41.4 +/- 0.5 degrees C vs 39.4 +/- 2.1 degrees C, p = 0.005). Furthermore, patients who died had significantly higher concentrations of blood urea nitrogen (8.7 +/- 2.1 vs 5.6 +/- 2.0 mmol/L, p = 0.01) and serum creatinine (212 +/- 71 vs 115 +/- 27 mumol/L, p = 0.033), and lower values of arterial pH (7.12 +/- 0.12 vs 7.34 +/- 0.10, p = 0.03), than those who survived. In the fatality group, the most common complication was rhabdomyolysis with acute renal failure (5 of 5); multiple organ failure resembling that from heatstroke was the leading cause of death from acute methamphetamine intoxication. In conclusion, the adverse prognostic features in patients with acute methamphetamine intoxication include coma, shock, convulsion, oliguria, and high core temperature. Acidosis, volume depletion, and ischemic renal damage were potential risk factors for development of acute renal failure in these patients.

Acute Disease↗

PubMed1998

[A study on methamphetamine psychosis in a psychiatric clinic--comparison of acute and chronic-type cases].

This study compares patients with acute methamphetamine psychosis to those with chronic methamphetamine psychosis and it investigates how the two groups differ in terms of psychosomatic findings, social background, and so on. The subjects consisted of 100 outpatients diagnosed at our clinic as having methamphetamine-induced psychosis over a period of sixteen years (1979 to 1995). Of these patients, 73 were of the acute type (currently using the drug or totally abstinent for less than 3 months), and 27 were of the chronic type (totally abstinent from the drug from 2 to 38 years). Psychosomatic Findings Ninety five patients (68 acute-type and 27 chronic-type) were classified into six clinical clusters, depending on which of the following states was dominant: paranoid-hallucinatory state, schizophrenia-like state, short-tempered and impulsive state, manic-depression-like state, neurosis-like state, and permanent-encephalopathic state. In the clinical cluster of paranoid-hallucinatory state, all 32 patients were of the acute-type. On the other hand, of those patients in the clinical cluster of neurosis-like state, the majority (N = 25) were of the chronic-type. Social Background The social background of 99 patients (72 acute-type and 27 chronic-type) was investigated under the three headings of: gangsters, criminal records and broken families. Of 19 patients who are gangsters, 18 cases were acute and the remaining case was chronic. Of 64 patients with criminal records, 51 were acute and 13 were chronic. Of 24 patients who come from broken families, 20 were acute and 4 were chronic. In all of these three items, the rate of acute-type patients was significantly higher than that of chronic-type patients. Based on the results obtained, the medical treatment and the prognosis of the patients, the author refers to preventive measures for stimulant-drug abuse.

Acute Disease↗

PubMed1999

Methamphetamine overdose: experience with six cases.

We describe experience with 6 cases of methamphetamine overdose. Because of its low cost, easy availability and longer duration of action compared to cocaine, methamphetamine has become the drug of choice in various communities. Marked change in mental status was observed in all of our patients. One patient had a myocardial infarction that responded well to thrombolytic therapy. Clinicians should be familiar with the medical effects and treatment of acute methamphetamine toxicity.

Adult↗

PubMed1999

The analysis of methamphetamine hydrochloride by thermal desorption ion mobility spectrometry and SIMPLISMA.

Ion mobility spectrometry (IMS) has been successfully developed to yield an advanced portable instrument. Such instruments may detect trace quantities of regulated substances at the crime scene. The atmospheric ion chemistry that occurs within the instrument may hinder the determination of analytes in real-world samples. The use of temperature programming adds an extra dimension to the data that improves the selectivity of the IMS data when chemometric processing is applied. The SIMPLISMA (SIMPLe-to-use-Interactive Self-Modeling Mixture Analysis) method is demonstrated for modeling variances in IMS data that are introduced from the temperature program. Methamphetamine hydrochloride IMS peaks are obscured by chemical interferences that arise from cigarette smoke residue. Cigarette smoke residue is pervasive at crime scenes. The ability of SIMPLISMA to resolve the analyte peaks that correspond to methamphetamine hydrochloride from interfering cigarette smoke has been demonstrated. A reduced mobility of 1.62 cm2V-1s-1 was observed for a methamphetamine hydrochloride monomer. With the IMS drift tube at room temperature, a second peak was observed at 1.24 cm2V-1s-1, which is consistent with a dimer ion. This peak has not been previously reported.

Central Nervous System Stimulants↗

PubMed1994

Effect of opioid peptides on dopamine release from nucleus accumbens after repeated treatment with methamphetamine.

The effect of opioid peptides on extracellular dopamine levels in the nucleus accumbens was compared between rats treated with methamphetamine and saline repeatedly (for 9 days) by using microdialysis. After the period of repeated treatment, the rats in both groups were kept for an additional 9 days without further treatment. Repeated administration of methamphetamine reduced the decreasing effect of dynorphin (10 microM), applied locally in the perfusate, and enhanced the increasing effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, 10 microM) on the extracellular dopamine levels in the nucleus accumbens. It is possible that repeated treatment with methamphetamine leads to attenuation of the inhibition and enhancement of the stimulation of dopamine release from the nucleus accumbens via presynaptic dynorphin- and enkephalin-sensitive receptors, respectively.

Analgesics↗