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At least 613 records · Page 34Linked to original sources

PubMed2000

Repeated adenosine pre-treatment potentiates the acute effect of methamphetamine in rats.

Adenosine was intraperitoneally (i.p.) injected to Wistar rats every 3 days with a total of 5 administrations. After a 7-day withdrawal, the animals were challenged with methamphetamine (0.5 mg/kg, i.p.). The effect of methamphetamine on locomotor activity was significantly potentiated by repeated adenosine pretreatment. Moreover, methamphetamine-induced dopamine release was also increased in the striatum. Methamphetamine-induced hyperactivity and dopamine release were significantly potentiated by repeated pretreatment of an adenosine A1 agonist, N6-cyclohexyladenosine (0.5 mg/kg, i.p.). These results suggest that the acute effect of methamphetamine is potentiated by repeated pre-treatment of adenosine via adenosine A1 receptors.

Adenosine↗

PubMed2005

Facilitative effect of a glutamate transporter inhibitor (2S,3S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy}aspartate on the expression of methamphetamine-induced behavioral sensitization in rats.

We examined the effects of a potent glutamate transporter inhibitor, (2S,3S)-3-{3-[4-(trifluoromethyl)benzoylamino]benzyloxy}aspartate (TFB-TBOA), on the expression of methamphetamine-induced behavioral sensitization in rats. Rats were intraperitoneally treated with 2 mg/kg methamphetamine for 5 days and then challenged with 1 mg/kg methamphetamine. Intracerebroventricular administration of TFB-TBOA (0.1 nmol) 10 min before the challenge significantly facilitated the expression of behavioral sensitization. On the other hand, it had no effect on the locomotor activation elicited by the challenge with methamphetamine in repeated-saline-treated (non-sensitized) rats. These results suggest that central glutamate transporters may play an inhibitory role in the expression of behavioral sensitization to methamphetamine.

Amino Acid Transport System X-AG↗

PubMed2002

Status of methamphetamine users 2-5 years after outpatient treatment.

Increasing numbers of methamphetamine users sought treatment during the decade of the 1990s. Little is known about the post treatment status of methamphetamine users who enter treatment. The data presented in this paper describe the outcome status of a group of a convenience sample of 114 methamphetamine users from a total group of 500 methamphetamine users who were treated 2-5 years prior to a follow up interview. Since the sample was not randomly selected, no specific treatment outcome attribution is possible. Methamphetamine use and other drug use of the follow up sample was substantially reduced from pretreatment levels. In general, the follow up status of the sample was much improved as compared to before treatment. However, headaches and depression were reported at a similar rate at follow up as had been reported at treatment admission.

Adult↗

PubMed2005

Barriers and pathways to diffusion of methamphetamine use among African Americans in the rural South: preliminary ethnographic findings.

There are no studies of African Americans methamphetamine use in the South where it is widespread among whites. We describe factors that inhibit or facilitate the diffusion of methamphetamine use among African Americans based on qualitative interviews with 86 drug users in rural Arkansas and Kentucky. Results suggest low prevalence of methamphetamine use among African Americans, and interviewees cited several barriers to its diffusion which were linked to the drug's ingredients, psychoactive and physiological effects, difficulty in accessing distribution networks, and established African-American preference for cocaine. Fourteen African Americans reported methamphetamine use and discussed pathways to it. Possible increases in African- American methamphetamine use merits further investigation.

Adult↗

PubMed2005

Selective disruption of nucleus accumbens gating mechanisms in rats behaviorally sensitized to methamphetamine.

Behavioral sensitization of psychostimulant-induced locomotor activity in rats has been proposed as a model of addiction and is accompanied by neuroadaptations in the nucleus accumbens and related circuits. Here, we used in vivo intracellular recordings to examine electrophysiological properties of accumbens neurons from animals that did or did not exhibit behavioral sensitization after repeated methamphetamine (5.0 mg/kg; 5 d). Although spontaneous activity of accumbens neurons was virtually unchanged, multiple synaptic interactions controlling membrane potential states were disrupted in sensitized animals. For example, stimulation of the ventral tegmental area attenuated accumbens responses to prefrontal cortex activation in nonsensitized and saline-treated animals, but not in sensitized animals. Acute methamphetamine (0.5 mg/kg) abolished accumbens up and down states in nonsensitized and saline-treated animals, suggesting a disruption of normal information processing in this area. However, acute methamphetamine failed to affect this pattern in accumbens neurons from sensitized animals. These results suggest that both acute and repeated methamphetamine administration can disrupt synaptic interactions in the nucleus accumbens; however, the nature of these alterations depends critically on the extent of behavioral sensitization. It is speculated that the response to acute methamphetamine in nonsensitized and saline-treated animals may be functionally adaptive, whereas the neuroadaptations observed in sensitized animals may be maladaptive and detrimental to accumbens information processing.

Animals↗

PubMed2004

Exploring the prevalence and correlates of methamphetamine use: findings from Sacramento's ADAM program.

Anecdotal reports have suggested that the use and abuse of methamphetamine is increasing in the United States. To date, however, few scholarly works have explored the prevalence and correlates of methamphetamine use in the United States. To address this limitation, a secondary analysis was undertaken with data collected through the Arrestee Drug Abuse Monitoring (ADAM) Program. An examination of methamphetamine-positive rates among ADAM arrestees interviewed between 1991 and 2001 identified that its use is concentrated within the Western part of the United States. Supplementary analyses of Sacramento arrestees indicated that 71% were diagnosed as needing some form of alcohol or other drug treatment. Compared to those arrestees who were detected methamphetamine-negative, methamphetamine-positive arrestees in Sacramento were three times as likely to be white and to have been diagnosed in need of drug treatment. Implications for drug control policy are discussed.

Adult↗

PubMed1984

Studies on N-demethylation of methamphetamine by liver microsomes of guinea-pigs and rats: the role of flavin-containing mono-oxygenase and cytochrome P-450 systems.

Relative participation of flavin-containing mono-oxygenase and cytochrome P-450 systems in N-hydroxylation of and formaldehyde release from methamphetamine were studied in vitro using liver microsomes of guinea-pigs and rats. In guinea pigs, only methimazole, an inhibitor of flavin-containing mono-oxygenase, significantly suppressed the above reactions. Formaldehyde release from methamphetamine was significantly inhibited not only by methimazole but also by inhibitors of the cytochrome P-450 system in liver microsomes from rats, but not guinea-pigs. Pretreatment of guinea-pigs with phenobarbital and 3-methylcholanthrene did not enhance the metabolism of methamphetamine. Pretreatment of rats with phenobarbital but not 3-methylcholanthrene increased slightly the N-demethylation of methamphetamine by liver microsomes. The results indicate that a marked species difference exists in the enzymes concerned with N-demethylation of methamphetamine. N-Oxidation predominates in guinea-pigs, whereas in rats, N-oxidation and C-oxidation of the methyl group participate equally as the initial reaction of the N-demethylation pathway.

Animals↗

PubMed1987

A new metabolite of methamphetamine; evidence for formation of N-[(1-methyl-2-phenyl)ethyl]ethanimine N-oxide.

1. N-Hydroxyamphetamine and N-hydroxymethamphetamine, metabolic intermediates of amphetamine and methamphetamine, showed no reactivity towards endogeneous protein, amino acids, nucleic acids and fatty acids. In contrast, formaldehyde, acetaldehyde and propionaldehyde reacted well with N-hydroxyamphetamine and slightly with N-hydroxymethamphetamine under mild conditions (pH 7.4, 37 degrees C). 2. Two products were isolated from the reaction mixture of acetaldehyde and N-hydroxyamphetamine. These were characterized as N-[(1-methyl-2-phenyl)ethyl]ethanimine N-oxide and N-[(1-methyl-2-phenyl)ethyl]butenimine N-oxide by mass and n.m.r. spectrometries. 3. N-[(1-Methyl-2-phenyl)ethyl]ethanimine N-oxide was formed by incubating methamphetamine with liver 9000 g supernatants of rats and guinea-pigs. The butenimine N-oxide derivative, however, could not be detected as a metabolite of methamphetamine in vitro. 4. N-[(1-Methyl-2-phenyl)ethyl]ethanimine N-oxide was also detected as a urinary metabolite of methamphetamine in rats and guinea-pigs. Thus, the ethanimine N-oxide was established as a novel metabolite of methamphetamine.

Amphetamine↗

PubMed1999

Methamphetamine and the expanding complications of amphetamines.

During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse.

Amphetamine-Related Disorders↗

PubMed2000

Cocaine and methamphetamine: differential addiction rates.

Clients admitted to treatment centers for stimulant addiction were categorized as either regular users of cocaine or of methamphetamine based on an algorithm involving 5 specific criteria. A subsample consisting of 90 regular users of cocaine and nonusers of methamphetamine, and 39 regular users of methamphetamine and nonusers of cocaine, was selected for comparison. Analyses showed that, when compared with cocaine users, the methamphetamine users exhibited a shorter period of time from 1st use to regular use (period of initial use) and from 1st use to treatment entry (period of pretreatment use). Relative to cocaine use, the use of methamphetamine appears to induce a faster rate of progression toward regular use and subsequent need for treatment.

Adult↗

PubMedDate not supplied

Pharmacokinetics of oral methamphetamine and effects of repeated daily dosing in humans.

The pharmacokinetics of orally administered S-(+)-methamphetamine-d3 were investigated in human male volunteers before and after a 13-day course of a slow release form of S-methamphetamine hydrochloride. A one-compartment pharmacokinetic model incorporating a lag time fits the data best. The average elimination half-life was 10.1 hr (range of 6.4-15.1 hr). There were no statistically significant differences in pharmacokinetic parameters when a low dose (0.125 mg/kg) was given before and after the 13-day oral regimen. When a higher challenge dose (0.250 mg/kg) was used, the maximum plasma concentration of methamphetamine-d3 was slightly but significantly greater when the test dose was given at the end of the oral dosing period than when it was given at the beginning. Although minor differences in pharmacokinetics occur after subchronic treatment with low doses of methamphetamine, their result would be to increase plasma concentration of the drug. Therefore, development of pharmacodynamic tolerance to methamphetamine could not be explained on the grounds of a change in pharmacokinetics.

Administration, Oral↗

PubMed1992

5-HT3 receptor antagonists block cocaine- and methamphetamine-induced place preference.

The effects of 5-HT3 receptor antagonists, MDL72222 and ICS205-930, on cocaine- and methamphetamine-induced place preference were examined. Cocaine (0.5-4.0 mg/kg, ip) and methamphetamine (0.25-2.0 mg/kg, ip) induced a dose-dependent place preference. The cocaine (4 mg/kg)-induced place preference was blocked by both MDL72222 and ICS205-930 (0.1 mg/kg, ip). On the other hand, the dose (0.1 mg/kg) of 5-HT3 antagonists did not block the methamphetamine (2 mg/kg)-induced place preference, although a higher dose (1.0 mg/kg) of 5-HT3 receptor antagonists did block it. The difference in sensitivity may reflect a difference in attack point in dopaminergic system of these two psychostimulants. Our findings suggest that the rewarding effects of cocaine and methamphetamine may be indirectly regulated by 5-HT3 receptor; cocaine being more sensitive to 5-HT3 receptor antagonists than methamphetamine.

Animals↗

PubMed2004

Acute coronary syndrome and crystal methamphetamine use: a case series.

"Ice" is a form of methamphetamine commonly used as a recreational drug in Hawaii and the Philippines, but seldom encountered in the continental United States. It differs in appearance from methamphetamine tablets, but otherwise has exactly the same molecules, only arranged in a crystalline structure. A sizeable body of in vitro, animal, and autopsy data suggest a linkage between methamphetamine use and myocardial pathology. In this report, we describe a series of eight patients who developed unstable angina or acute myocardial infarction in association with smoking crystal methamphetamine. The findings, to a large extent, resemble those with cocaine-associated acute coronary syndromes. Given the widespread abuse of methamphetamine among young age groups, the recognition and primary prevention of cardiovascular toxic effects is of mounting socioeconomic importance.

Acute Disease↗

PubMed1991

Simultaneous analysis of amphetamine, methamphetamine, and 3, 4-methylenedioxymethamphetamine (MDMA) in urine samples by solid-phase extraction, derivatization, and gas chromatography/mass spectrometry.

A rapid and effective solid-phase extraction procedure using Bond Elute Certify bonded silica sorbent cartridges was adopted to extract amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) from urine samples. The extract was derivatized with trichloroacetic anhydride prior to gas chromatography/mass spectrometry (GC/MS) analysis with selected ion monitoring of the following ions: 190, 91, 188; 204, 91, 202; 162, 135, 202; 194, 123; and 211, 209 for the derivatized amphetamine, methamphetamine, MDMA, d5-amphetamine, and d9-methamphetamine, respectively. The first of the ions listed for each compound was used for quantitation. The compound d5-amphetamine was used as the internal standard for amphetamine, and d9-methamphetamine was used for methamphetamine and MDMA. Results showed a higher than 65% recovery and a reproducibility with less than a 5% coefficient of variation. When a sample size of 2 mL was used, the lowest detectable concentration was about 50 ng/mL, and a near-perfect fit can be obtained (within the 250 to 4000-ng/mL concentration range studied) using a second-order polynomial model.

3,4-Methylenedioxyamphetamine↗

PubMed1989

Evidence for dual mechanisms involved in methamphetamine-induced increases in striatal preprotachykinin mRNA.

The mechanism(s) whereby the indirect dopamine agonist methamphetamine causes a 2-3-fold increase in rat striatal preprotachykinin (PPT) mRNA was investigated. It was determined that the increase in PPT mRNA levels following a single injection of 5 mg of methamphetamine/kg of body weight was initiated in the cell nucleus, ruling out cytoplasmic PPT mRNA stabilization as a primary mechanism for this increase. It was established with T1 nuclease/RNA protection protocols that methamphetamine injection increased mature PPT message approximately 3-fold over a 2-h period, and this increase was sustained for at least 4 h after drug treatment. Striatal content of the PPT gene primary transcript (containing transcribed introns) was decreased by 50% within 20 min and remained suppressed for at least 4 h post-methamphetamine. Nuclear transcription assays indicated a 2-3-fold increase in the rate of gene transcription that lasted 60-90 min after methamphetamine treatment; by 2 h the transcription rate had returned to control levels. Taken together, these changes and their time courses suggest the indirect dopamine agonist alters striatal PPT gene expression at two levels: 1) a transient increase in the rate of PPT gene transcription and 2) a more sustained increase in the rate at which PPT hnRNA is processed to mature PPT mRNA. It is unclear whether these two changes are linked or are independent modes of action by methamphetamine.

Animals↗

PubMed1987

Single-reagent polarization fluoroimmunoassay of methamphetamine in urine.

We developed a polarization fluoroimmunoassay for the specific detection of methamphetamine in urine. Sheep antiserum raised against methamphetamine was premixed with a fluorescein-labeled amphetamine tracer in a single reagent. The use of labeled amphetamine gave a more sensitive and more specific assay than did the use of a labeled methamphetamine tracer. The assay system had equal sensitivity for the d- and l-isomers of methamphetamine while the cross reactivity of amphetamine and other structurally related compounds was 3% or less. With a positive/negative cutoff concentration set at 1 mg/L, the polarization fluoroimmunoassay reliably identified human urines that had been reported positive for methamphetamine by an established gas-liquid chromatographic method.

Animals↗

PubMed1977

["Methamphetamine-stereotypies" and brain dopamine levels of rats treated with single or repeated doses of alpha-methyl-para-tyrosine (author's transl)].

Male albino Wistar rats were injected intraperitoneally with saline solution (1.0 ml/kg) or a-methyl-paratyrosine (50 mg/kg) once or daily X 7 and methamphetamine (10 mg/kg) was injected 3 hr or 24 hr after the last injection of these drugs. Stereotyped licking and biting activity were scored during 120 min after methamphetamine injection and, in parallel brain dopamine levels were measured. Methamphetamine given 3 hr after single or repeated administrations of alpha-methyl-para-tyrosine was not effective for stereotyped behavior and brain dopamine levels in similarly treated rats decreased markedly in comparison with saline-treated rats. Methamphetamine 24 hr after repeated administration of alpha-methyl-para-tyrosine clearly induced stereotypies and brain dopamine levels in these rats did not differ from saline-treated rats. The results suggest a possible role of brain dopamine on "methamphetamine-stereotypies".

Animals↗

PubMedDate not supplied

Leuckart-specific impurities in amphetamine and methamphetamine seized in Norway.

Samples of 28 amphetamine and 7 methamphetamine seizures, taken in Norway from 1975 to 1982, were examined. The amphetamine and methamphetamine contents varied from 9 to 99 per cent and from 9 to 72 per cent respectively. Impurities originating from the synthesis of the illicit samples were identified by gas chromatography combined with mass spectrometry. Special attention was paid to "Leuckart-specific" impurities, which could indicate that the Leuckart method of amphetamine and methamphetamine synthesis had been used. N-formyl-methamphetamine, a Leuckart-specific compound, was identified in all the investigated samples of methamphetamine seized in Norway. The Leuckart-specific impurities, 4-methyl-5-phenyl-pyrimidine and N-formyl-amphetamine, were identified in 79 per cent of the amphetamine samples.

Amphetamine↗