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PubMed1982

Metabolism of (-) deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: a biochemical assessment.

The urinary excretion of some important phenylethylamines, catecholamines, their metabolites, amphetamine, and methamphetamine were measured in parkinsonian patients on Sinemet (L-dopa plus carbidopa, a peripheral dopadecarboxylase inhibitor) and depressed patients after chronic (-) deprenyl treatment. Deprenyl was efficiently metabolized to amphetamine and methamphetamine. It increased the excretion of phenylethylamine and of m- and p-tyramine, and reduced the output of norepinephrine metabolites, but failed to alter the excretion of dopamine-deaminated metabolites. These changes were attributed more to amphetamine and methamphetamine than to inhibition of monoamine oxidase type B. Sinemet treatment alone increased the excretion of dopamine, 3-methoxytyramine, and their respective deaminated metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid. It is concluded that conversion of deprenyl to amphetamine and methamphetamine may contribute to some of the therapeutic benefits of deprenyl.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1985

Effects of methamphetamine and methyldopa on ethanol induced hypothermia in mice.

The effects of D-methamphetamine HCl (1, 2 and 4 mg/kg, i.p.) and alpha-methyldopa (1, 2 and 4 mg/kg, i.p.) on rectal temperature and on ethanol (3 g/kg, i.p.)-induced hypothermia have been investigated in mice. Methamphetamine caused a dose-dependent hyperthermia, but methyldopa induced hypothermia, which decreased with increases in dose. Methamphetamine antagonized the hypothermic effect of ethanol, but methyldopa (1 and 2 mg/kg) did not affect it. Methyldopa (4 mg/kg), however, reversed ethanol hypothermia. Ethanol pretreatment significantly potentiated the hypothermic effect of methyldopa (4 mg/kg), and it prevented methamphetamine-induced hyperthermia. A possible central action for the tested drugs on biogenic monoamines and a peripheral component in their thermoregulatory effects are discussed in this report.

Animals↗

PubMed1989

Enhancement of ambulation-increasing effect of methamphetamine by peripherally-administered 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) in mice.

Behavioral effects of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP), a co-factor for tyrosine hydroxylase and tryptophan hydroxylase, were investigated by means of ambulatory activity in mice. Single administration of R-THBP (50 and 100 mg/kg, s.c.) showed no significant effect on the mouse's ambulatory activity for 5 hr. The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was dramatically enhanced and prolonged by the pretreatment with R-THBP (100 mg/kg, s.c.) 0, 2, 6, 12 and 24 hr before, but not 18 or 36 hr before, the methamphetamine administration. However, when combined administration of R-THBP (100 mg/kg, s.c., 2 hr before) with methamphetamine (2 mg/kg, s.c.) was repeated at intervals of 3-4 days, the enhancement by R-THBP of the methamphetamine effect was observed only in the 1st and 2nd administration, but not in the later administration. The pretreatment with R-THBP (100 mg/kg, s.c., 2 hr before) enhanced the ambulation-increasing effect of ephedrine (80 mg/kg, i.p.), but failed to modify those of cocaine (20 mg/kg, s.c.), mazindol (2.5 mg/kg, s.c.), bromocriptine (8 mg/kg, i.p.), morphine (20 mg/kg, s.c.) and scopolamine (0.5 mg/kg, s.c.). It is noteworthy that R-THBP differentially modifies the ambulation-increasing effect of the above-mentioned drugs.

Animals↗

PubMed1990

Effects of YM-09151-2, a potent and selective dopamine D2 antagonist, on the ambulation-increasing effect of methamphetamine in mice.

The ambulation-increasing effect of methamphetamine (2 mg/kg, s.c.) was markedly reduced by YM-09151-2 at 0.01 mg/kg, s.c., in drug-naive mice. The development of reverse tolerance to the ambulation-increasing effect of methamphetamine was also inhibited almost completely when 0.01 mg/kg, s.c., of YM-09151-2 was administered concomitantly in each administration. However, YM-09151-2, at 0.01 mg/kg, was partially suppressed the effect of methamphetamine in mice that exhibited reverse tolerance to methamphetamine.

Animals↗

PubMed2002

Will the methamphetamine problem go away?

Methamphetamine use has clearly reached epidemic proportions in large parts of the western and midwestern US. Because of the regional specificity of methamphetamine use, there is speculation that it may be a temporary problem and not a long-term public health problem. Unfortunately there are a number of factors that suggest that significant methamphetamine problems may persist or even expand. For this reason, it is important that federal law enforcement, prevention, research and treatment agencies prepare strategies to address the likelihood of this persisting problem. This article reviews the issues concerning the future of the methamphetamine problem in the US and provides some recommendations for setting priorities to address the problem.

Adult↗

PubMed1996

A quantity of stereotyped behavior of ddY mice induced by low-dose methamphetamine.

It is reported that high-dose methamphetamine (8 mg/kg) induces stereotyped behavior in ddY mice in an open field, but it is still not certain that low-dose methamphetamine (less than 2 mg/kg) can induce the stereotyped behavior in ddY mice in a narrow space. In order to investigate the problem, we evaluated the quantity of stereotyped behavior of ddY mice by using a mouse wheel-running apparatus. In this method, we have come to recognize an increase in the stereotyped behavior depending on the dose of methamphetamine and the reverse-tolerance phenomenon as a decrease in the wheel-revolution counts. The present findings indicate that low-dose methamphetamine can promote stereotyped behavior in ddY mice under conditions in which the ambulation is restricted to a narrow wheel space.

Animals↗

PubMed1989

Effects of SCH23390 injection into the dorsal striatum and nucleus accumbens on methamphetamine-induced gnawing and hyperlocomotion in rats.

The effects of SCH23390, a selective D1 receptor antagonist, injected into either the dorsal striatum or nucleus accumbens on methamphetamine-induced stereotyped gnawing and hyperlocomotion in rats were investigated. SCH23390 injected into the dorsal striatum did not alter the gnawing induced by both methamphetamine and apomorphine. However, SCH23390 injected into the nucleus accumbens significantly reduced methamphetamine-induced gnawing without altering the effects of apomorphine. Injection of SCH23390 into the nucleus accumbens reduced the hyperlocomotion produced by methamphetamine more markedly than injection of SCH23390 into the dorsal striatum.

Animals↗

PubMed1998

Ultrastructural findings of the endothelial cells in pancreatic lesions after chronic administration of methamphetamine in rats.

The effects of chronic administration of methamphetamine on the pancreas were studied using electron micrography in an experimental model. Methamphetamine (1 mg/kg/day) was subcutaneously injected in five-week-old male Wistar Kyoto rats (WKY) for 8 weeks. Five age and sex-matched WKY served as controls. In light microscopy, scattered necrosis, intercellular vacuolization and severe hemorrhage were the prominent lesions in the methamphetamine-treated rats. The associated ultrastructural alterations consisted of degenerated, swollen, mitochondria with disrupted cristae and cell debris in the superficial space of the endothelial cells, and extensive vacuolization in the degenerated endothelial cells of small vessels and in the smooth muscle cells of their wall. However, in this study, hypercontration or lamellar membrane-like changes were not identified. It is suggested that pancreatic necrotic hemorrhage is a consequence of methamphetamine damage to endothelial cells in various organs, including pancreas.

Animals↗

PubMed1985

Distribution and excretion of methamphetamine and its metabolites in rats. III. Time-course of concentrations in blood and bile, and distribution after intravenous administration.

The time-course of blood total radioactivity after i.v. administration of 3H-methamphetamine to rats showed a biphasic curve. The biological half-life of the alpha phase (t alpha 1/2) was 6.8 +/- 2.0 min, and that of the beta phase (t beta 1/2) was 11.3 +/- 0.8 h. The major metabolite in the blood was unconjugated p-hydroxymethamphetamine. The total radioactivity in bile peaked at 1.5 h after i.v. administration. The major metabolite in the bile was p-hydroxymethamphetamine glucuronide. The major compound excreted in urine was unchanged methamphetamine. Whole-body autoradiography was performed using 14C-methamphetamine, and tissue 3H concn. was determined after i.v. administration of 3H-methamphetamine to rats.

Animals↗

PubMed1988

Participation of cytochrome P-450 isozymes in N-demethylation, N-hydroxylation and aromatic hydroxylation of methamphetamine.

1. Five isozymes of cytochrome P-450 were purified from liver microsomes of phenobarbital-pretreated (P-450-SD-I and -II), 3-methylcholanthrene-pretreated (P-450-SD-III) and untreated rats (P-450-SD-IV and -V) to determine their catalytic activities in metabolic reactions of methamphetamine. 2. All the isozymes except P-450-SD-III showed considerably high N-hydroxylating activity of methamphetamine. The cytochromes P-450 initiate N-demethylation of this drug by two metabolic pathways, C-hydroxylation and N-hydroxylation. 3. Both N-demethylation and N-hydroxylation of methamphetamine were efficiently catalysed by the phenobarbital-inducible forms P-450-SD-I and -II and constitutive forms P-450-SD-IV and -V. 4. The constitutive forms P-450-SD-IV and -V revealed high catalytic activities of p-hydroxylation of methamphetamine, but phenobarbital- and 3-methylcholanthrene-inducible isozymes showed only low activities. 5. The present results indicate that the different extents of the metabolic intermediate complex formation with cytochrome P-450 (455 nm complex) in the microsomes from phenobarbital-, 3-methylcholanthrene-pretreated, and untreated rats is not attributable to the activities of the respective isozymes of cytochrome P-450 to form the precursor of the complex, N-hydroxymethamphetamine.

Animals↗

PubMed2000

Public health consequences among first responders to emergency events associated with illicit methamphetamine laboratories--selected states, 1996-1999.

Methamphetamine, a central nervous system stimulant, is manufactured in illicit laboratories using over-the-counter ingredients. Many of these ingredients are hazardous substances that when released from active or abandoned methamphetamine laboratories can place first responders at risk for serious injuries and death. In 16 states, the Agency for Toxic Substances and Disease Registry maintains the Hazardous Substances Emergency Events Surveillance (HSEES) system to collect and analyze data about the morbidity and mortality associated with hazardous substance-release events. Based on events reported to HSEES during 1996-1999, this report describes examples of events associated with illicit methamphetamine laboratories that resulted in injuries to first responders in three states, summarizes methamphetamine-laboratory events involving injured first responders, and suggests injury prevention methods to protect first responders.

Accidents↗

PubMed2001

Acute respiratory distress syndrome in a woman with heroin and methamphetamine misuse.

Methamphetamine, heroin, and cannabis are three of the most commonly misused drugs in Asia. In Taiwan, cases of misuse of methamphetamine have been increasing. In this paper, we report the case of a 23-year-old woman who had a 10-year history of smoking methamphetamine and intermittent use of heroin for 3 to 4 years. She developed pulmonary toxic effects associated with misuse of heroin and methamphetamine. She was brought to the emergency room because of consciousness disturbance and acute respiratory failure. Her symptoms of rapid progression of refractory hypoxemia, ill-defined densities over both lung fields, and normal pulmonary artery wedge pressure were consistent with acute respiratory distress syndrome. Rapid resolution of infiltrations and improvement of oxygenation were observed after mechanical ventilation with positive end-expiratory pressure support and oxygen therapy. She was discharged on the fifteenth hospital day without any sequela except for mild exertional dyspnea.

Adult↗

PubMed1975

[Clinical-pharmacological studies on the effect of mephentermin and methamphetamine on the hemodynamics of the lung circulation].

In haemodynamic investigations of altogether 40 male probands with normal and restricted functional capacity of the lungs the result of an intravenous injection of mephentermine (30 mg) or methamphetamine (15 mg) was a transient increase of the mean pressure in the pulmonary artery and of the resistance of the pulmonary vessels. Temporarily parallel the arterial mean pressure and the resistance of the vessels in the greater circulatory system in most cases increased by about the same, in healthy persons after application of methamphetamine by a smaller relative amount. In the dosage used the vasoconstrictive effect of methamphetamine was altogether only somewhat more expressed. At the time of the maximum increase of the mean pressure of the pulmonary artery in healthy persons methamphetamine had a negative chronotropic and inotropic effect. It is referred to practical therapeutic consequences.

Adult↗

PubMed1992

The adverse effects of l-methamphetamine on the development of explanted rat embryos.

The adverse effects of l-methamphetamine on the development of rat embryos were studied by means of a whole culture system. The embryos explanted at 12.5th days of gestational age were cultured for a total of 24 hours. After pre-culturing for 6 hours, 4 groups of embryos received additional culturing for 18 hours with saline or various concentrations of l-methamphetamine; 0.5, 2.0 and 5.0 mumol/dl. There was no significant difference in the survival rate among 4 groups. The groups over 2.0 mumol/dl of l-methamphetamine showed significant reduction of crown-rump length, somite number, protein content, DNA content, and protein/DNA ratio. It is suggested that over 2.0 mumol/dl of l-methamphetamine reduces the development but not the survival of rat embryos under whole culture system.

Animals↗

PubMed2003

[Candidate genes or compounds for therapeutic tools against methamphetamine and/or morphine-induced dependence].

Drug dependence is one of most severe problems in all over the world, however, the mechanisms and related-genes have not been completely revealed. Here we would like to introduce tumor necrosis factor-alpha (TNF-alpha). Repeated treatment with methamphetamine induced an increase in TNF-alpha mRNA in the some brain regions. Exogenous TNF-alpha blocked the methamphetamine rewarding. TNF-alpha plays a neuroprotective role in methamphetamine drug dependence. These results suggest that TNF-alpha is one of key proteins. TNF-alpha itself might not be therapeutic tools, since it has immunological actions in physical conditions. Therefore, next, we found a stimulator, Leu-Ile, which enhances TNF-alpha synthesis in cultured neurons. Leu-Ile protected blocked the methamphetamine induced rewarding effects. These results suggest that a stimulator of TNF-alpha synthesis may be one of therapeutic tools against drug dependence.

Animals↗

PubMed2004

[GC-MS analysis of methamphetamine and amphetamine in hair of Thai drug addicts].

UNLABELLED: Psycho-stimulant dependence in young individuals has become a serious problem in Thailand, where consumption of the so-called YaBa methamphetamine tablets has become a fashionable trend. Due to its easy availability in the form of a tablet, young individuals abuse methamphetamine. Methamphetamine tablets are known to be potently addictive and its difficulty in cessation of drug use and to be abstinent from the drug. We herein report the results obtained from GC-MS analysis of methamphetamine and amphetamine in 33 samples of urine and hair from patients with psycho-stimulant dependence. These samples were collected from patients registered at the outpatient clinic in the Department of Psychiatry, Chiang Mai University Hospital and were sent to Nippon Medical School, Department of Legal Medicine (Tokyo, Japan) for further analysis by Dr. Werawan Ruangyttikarn, Department of Forensic Medicine, Chiang Mai University. Sample preparation: Hairs samples were cropped near the hair root. After washing, they were cut into 1.2-cm sections and extracted with methanol/5N HCl (2:1) for an hour and then, solid-phase extraction was conducted using Bond-Elut Certify. Following extraction, GC-MS analysis was performed. Urine samples were subjected to GC-MS analysis after preparation with Bond Elut Certify. RESULTS AND DISCUSSION: In 6 samples, both urine and hair samples analyzed were negative for detection of the stimulant drugs. In those cases individuals might stop taking drug for about 5 months. In 18 samples, urine samples were negative whereas hair samples were positive. These results suggest that individuals might stop using drugs for a few days before they went to the hospital but they abuse drugs continuously. In 9 samples, both urine and hair samples were positive. These results show that individuals always abuse drugs. In order to treat drug dependence effectively it is necessary to obtain the patient history of drug use and to evaluate and determine short-term and long-term drug use with urinalysis and hair analysis, respectively. Our present data revealed that useful information concerned with the long term drug abuse can be obtained from hair analysis, and that this method of analysis is applicable not only to forensic cases but also for evaluating clinical cases.

Adolescent↗

PubMed2005

[Control of craving for methamphetamine: development of scales for dependence and search for medicines for treatment].

Methamphetamine dependence presents a serious problem not only for patients but also for society. Medical treatment has mainly targeted psychotic symptoms such as hallucination and delusion, and ignored the symptoms of craving, which are the major cause of dependence. Therefore, the risk of lapse into methamphetamine reuse remains very high. Although development of both medicines and programs for treatment of craving is needed, progress has been hampered by the lack of appropriate scales for assessing the severity of dependence and craving. On the other hand, recent breakthroughs in genomic sciences and molecular medicine have made it possible to investigate the molecular mechanisms underlying craving in animals. This paper reviews studies on the development of scales for assessing the severity of methamphetamine dependence and craving, together with recent data on candidate medicines for craving treatment in animals. The reliability and validity of the revised Addiction Severity Index -Japanese version (ASI-J) was confirmed after its administration to 100 drug abuse patients. The Craving Index was also newly developed, and its validity for prediction of relapse was confirmed. In animal experiments, fluoxetine, a selective serotonin reuptake inhibitor, was recognized as a candidate medicine for treatment of methamphetamine dependence.

Animals↗

PubMedDate not supplied

The methamphetamine epidemic and dentistry.

Methamphetamine is a potent central nervous system stimulant with limited therapeutic effects. This drug produces prolonged euphoria and is relatively inexpensive to purchase and easy to make and distribute. Methamphetamine changes normal physiologic processing of several centrally acting neurotransmitters and ultimately leads to neurotoxicity and neurodegeneration from chronic use. Chronic methamphetamine use has been associated with severe oral health effects; rampant caries is the most notable of these. Dental professionals must recognize patients who are involved with methamphetamine use and understand the risk factors associated with its deleterious oral effects so that preventive and treatment strategies may be implemented for patients who use this drug.

Adolescent↗