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PubMedDate not supplied

Multiplex assay of amphetamine, methamphetamine, and ecstasy drug using CEDIA technology.

Using Microgenics unique technology, cloned enzyme donor immunoassay (CEDIA), the multiplex assay (CEDIA Amphetamines/Ecstasy) has been developed for the detection of amphetamine, methamphetamine, and ecstasy drugs at cutoff level either of 500 ng/mL or 1000 ng/mL applicable for either qualitative screening or semiquantitative measurement. The multiplex assay detects the total concentration of amphetamine, methamphetamine, and ecstasy drugs in urine samples. In addition, the assay detects metabolites of parent drugs and structurally related drugs including d,l-amphetamine (67.2%), d,l-methamphetamine (58.4%), MDA (113%), MDMA (199%), MDEA (207%), MBDB (123%), BDB (72%), PMA (24%), and PMMA (100%). The assay is highly specific and exhibits minimal cross-reactivity with the undesirable, structurally related over-the-counter amphetaminelike drugs. Imprecision results (n = 120) demonstrate an intra-assay < 6.3% CV and an interassay < 9.2% CV as performed by a modified NCCLS protocol. Using the SAMHSA mandatory guidelines of a 500-ng/mL cutoff for the immunoassay and a 250-ng/mL cutoff for GC-MS, the assay detects 164 out of 165 GC-MS-positive samples. For drug abuse testing, the multiplex assay presents an excellent method for the detection of multiple drugs with greater sensitivity and broader detection.

Amphetamine↗

PubMed2002

Quantitative analysis of selegiline and three metabolites (N-desmethylselegiline, methamphetamine, and amphetamine) in human plasma by high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

This report describes a sensitive and specific high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry method for the detection of subnanogram concentrations of selegiline and its three principle metabolites, N-desmethylselegiline, methamphetamine, and amphetamine, in human plasma. The assay has a dynamic range of 0.1-20 ng/mL for selegiline and N-desmethylselegiline (norselegiline) and 0.2-20 ng/mL for methamphetamine and amphetamine. The inter- and intra-assay precision and accuracy varied by less than 11% for all analytes at 0.3, 2.5, and 15 ng/mL and less than 16% at the lower limit of quantitation (0.1 ng/mL for selegiline and norselegiline; and 0.2 ng/mL for methamphetamine and amphetamine). Selegiline and its metabolites showed no significant loss in quantitative accuracy after three freeze/thaw cycles or after up to 6 h at room temperature prior to extraction. Extracted plasma samples retained quantitative accuracy after storage for at least 7 days at -20 degrees C or up to 70 h at room temperature. Methanolic stock solutions were stable for at least 6 h when kept at room temperature or at least 90 days when kept at -20 degrees C.

Amphetamine↗

PubMed2005

Determination of l-methamphetamine: a case history.

Methamphetamine was detected in a 77-year-old male who had a history of congestive heart failure. Using a modification of a previously reported method, trifluoroacetyl-l-prolyl chloride was used to derivatize sympathomimetic amines to allow separation and identification of individual enantiomers. The l-enantiomer of methamphetamine and a trace amount of l-amphetamine were found in blood and urine specimens from this case. Further investigation revealed the decedent had bronchial asthma and regularly used a Vicks Inhaler, which contains l-methamphetamine as the active ingredient.

Administration, Inhalation↗

PubMed2004

Methamphetamine abuse and manufacture: the child welfare response.

Methamphetamine abuse is on the rise, particularly by women of childbearing age. This article describes the history and effects of methamphetamine use. The authors examine the ways exposure to the manufacture of this drug affects clients and social workers in the course of their work. Because children are frequently found at the scene of a manufacturing laboratory, the child welfare system often becomes involved, and child protective services and other social work agencies need protocols to address the needs of the children and their parents, as well as those of the legal system. In 1997 California created and implemented drug-endangered children's units in seven counties to address the needs of children from families that manufacture methamphetamine; these units involve collaborative efforts among child protective workers, district attorneys, physicians, and police officers. A case example provides information about the role of social workers and their collaboration with these multiple systems.

Adult↗

PubMed1996

Increased Gi alpha and Go alpha mRNAs in hippocampus after repeated methamphetamine administration.

Changes in transcription of Gs alpha, Gi2 alpha and Go alpha proteins after repeated methamphetamine administration were investigated using in situ hybridization. Rats received daily injections of methamphetamine (4 mg kg-1) for 14 days. Four hours after the last injection, Go alpha mRNA showed an increase of 16.6-31.6% in CA1, CA3 and dentate gyrus of the hippocampus. Gi alpha mRNA level increased by 24.2% in CA1, while Gs alpha mRNA remained unaffected. Go alpha and Gi alpha mRNA returned to basal levels after 48 h abstinence. The expression of these G alpha mRNA in other brain regions, including substantia nigra, ventral tegmentum area, striatum, accumbens and cortices, was unchanged. The increase in Go alpha and Gi alpha mRNAs restricted only to the hippocampus after repeated methamphetamine administration may be involved in the development of dependence rather than behavioral sensitization.

Animals↗

PubMed2000

Reinforcing effects of methamphetamine in planarians.

Reinforcing properties of dopamine agonist, methamphetamine, for planarians were examined with the conditioned place preference (CPP) procedure. The planarians showed preference for the environment associated with methamphetamine administration. This reinforcing effect was antagonized by pretreatment with non-selective dopamine antagonist, haloperidol. Both selective D1 antagonist SCH23390 and selective D2 antagonist sulpiride also blocked the reinforcing effect of methamphetamine. These results suggest that reinforcing effects of dopaminergic drugs can be traced back to invertebrates such as planarians.

Amphetamine-Related Disorders↗

PubMed1988

Design and development of a single-reagent polarization fluoroimmunoassay for methamphetamine.

The design and development of reagents suitable for use in single-reagent polarization fluoroimmunoassay of methamphetamine is described. The single-reagent method requires that a substantial fraction of antibodies exhibit fast dissociation of bound tracer. Antiserum obtained early in the course of immunization of a sheep with a methamphetamine immunogen had suitable dissociation characteristics. Tracers with bridges of different length between methamphetamine and the fluorescein label group were prepared and evaluated. A single-reagent assay with sensitivity and specificity suitable for urine screening application was demonstrated.

Animals↗

PubMed2006

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

OBJECTIVE: To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. METHODS: We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. RESULTS: Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. CONCLUSIONS: In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Benzodiazepines↗

PubMed2007

Frequent methamphetamine use is associated with primary non-nucleoside reverse transcriptase inhibitor resistance.

We determined whether methamphetamine use is associated with the increased prevalence of primary HIV drug resistance among a cohort of men who have sex with men recently infected with HIV. In multivariate analysis, we found that frequent methamphetamine use was strongly associated with primary non-nucleoside reverse transcriptase inhibitor resistance, but not with protease inhibitor or nucleoside reverse transcriptase inhibitor resistance. We postulate that this association may be caused by methamphetamine-associated treatment interruptions among source partners.

Adult↗

PubMed1988

Effects of chronic treatment of methamphetamine and imipramine on amygdaloid seizure's generation.

We assessed the effects of chronic treatment of methamphetamine (1-2 mg/kg/day, i.p., 17 days) and imipramine (2-8 mg/kg/day, p.o., 17 days) on amygdala-generating seizures using the kindling method induced by low-frequency electrical stimulations. The number of stimulating pulses required for the triggering of epileptic afterdischarge (pulse-number threshold: PNT) is the indicator of seizure generating threshold. A PNT elevation followed by its reduction occurred, compared to the pretreatment level, during a 2 mg/kg/day chronic methamphetamine treatment. A reduction in the PNT and triggered afterdischarge durations occurred during a chronic imipramine treatment. These results indicate that both methamphetamine and imipramine reduced the seizure generating threshold by repeated applications. It is suggested that this finding might be related to the psychoactive potency and associated neurochemical changes which are known to be caused by these drugs.

Amygdala↗

PubMed1999

Effect of methamphetamine on male mice fertility.

The effect of methamphetamine (MAMP) on the ability of males to mate with females and to impregnate them was examined in 8-week-old ICR mice. Male mice that had been administered an intraperitoneal injection of MAMP (15 mg/kg, 7.5 mg/kg, or 3.75 mg/kg) or saline were housed with females 24 or 48 hours later. The vaginal plugs were checked, and the number of births was counted. The effect of MAMP on sperm motility and the serum testosterone (TS) concentration was also examined. Methamphetamine was observed to have harmful effects only at the highest dose level. In the mice housed 24 hours after the injection of 15 mg/kg MAMP, the increase in the cumulative number of vaginal plugs lagged, and the total number of vaginal plugs decreased significantly. A significant decrease was also observed in the total number of births. Methamphetamine, at a dose of 15 mg/kg, decreased sperm motility. The TS concentration decreased initially, then increased.

Animals↗

PubMed1985

Effect of ergometrine on methamphetamine and apomorphine stereotypy in the guinea-pig.

Pretreatment with the DAi receptor antagonist ergometrine (10, 20 mg kg-1 i.p.) significantly potentiated methamphetamine stereotypy and facilitated the induction of biting, gnawing or licking behaviour by amantadine. However, ergometrine (5-20 mg kg-1) did not significantly influence the stereotyped behaviour induced by the DAe receptor agonist apomorphine. The results suggest that the DAi antagonist ergometrine is effective in modifying the behaviours induced by methamphetamine and amantadine, agents which through released DA simultaneously activate both DAe and DAi receptors, but fails to modify the stereotyped behaviour induced by apomorphine which specifically activates only DAe receptors. However, the possibility that ergometrine might have potentiated methamphetamine stereotypy and facilitated the induction of biting, gnawing or licking behaviour by amantadine through modulation of the activity of the central noradrenergic and 5-hydroxytryptaminergic systems, which are reported to influence DA-mediated behaviours, also needs to be considered.

Amantadine↗

PubMed1998

Importance of initial environments in the development of ambulatory sensitization to methamphetamine and cocaine in mice.

Repeated administration of CNS stimulants such as amphetamines and cocaine induces behavioural sensitization which can be influenced by the animal's environment. This study has evaluated the effect of restraint on the development and maintenance of ambulatory sensitization to methamphetamine and cocaine in mice. Subcutaneous administration of the CNS stimulants methamphetamine (2 mg kg(-1)) and cocaine (20 mg kg(-1)) seven times at three-day intervals resulted in ambulatory sensitization when the mice were placed in 20-cm diameter activity cages after each dose of the drug. However, if methamphetamine or cocaine was administered when the mice were in small jars (6-cm diameter) in which expression of ambulation, but not of circling and rearing, was completely restricted, the development of ambulatory sensitization was retarded or inhibited, with circling behaviour concurrently increased, when subsequent repeated doses of the drug were administered in the activity cage. Subsequent repeated treatment of ambulatory-sensitized mice with the drug or saline when the mice were in the jars did not change the levels of the ambulatory sensitization or the circling behaviour. These results suggest that the mice are sensitized to the behavioural effect of CNS stimulants which can be expressed in the environment in which the drug is administered. It is also considered that the established sensitization is strongly retained and is responsible for retardation or suppression of the development of sensitization to other behavioural stimulant effects.

Animals↗

PubMed2006

Methamphetamine-induced sensitization differentially alters pCREB and DeltaFosB throughout the limbic circuit of the mammalian brain.

Enhancements in behavior that accompany repeated, intermittent administration of abused drugs (sensitization) endure long after drug administration has ceased. Such persistence reflects changes in intracellular signaling cascades and associated gene transcription factors in brain regions that are engaged by abused drugs. This process is not characterized for the most potent psychomotor stimulant, methamphetamine. Using motor behavior as an index of brain state in rats, we verified that five once-daily injections of 2.5 mg/kg methamphetamine induced behavioral sensitization that was demonstrated (expressed) 3 and 14 days later. Using immunoblot procedures, limbic brain regions implicated in behavioral sensitization were assayed for extracellular signal-regulated kinase and its phosphorylated form (pERK/ERK, a signal transduction kinase), cAMP response element binding protein and its phosphorylated form (pCREB/CREB, a constitutively expressed transcriptional regulator), and DeltaFosB (a long-lasting transcription factor). pERK, ERK, and CREB levels were not changed for any region assayed. In the ventral tegmental area, pCREB and DeltaFosB also were not changed. pCREB (activated CREB) was elevated in the frontal cortex at 3 days withdrawal, but not at 14 days. pCREB levels were decreased at 14 days withdrawal in the nucleus accumbens and ventral pallidum. Accumbal and pallidal levels of DeltaFosB were increased at 3 days withdrawal, and this increase persisted to 14 days in the pallidum. Thus, only the ventral pallidum showed changes in molecular processes that consistently correlated with motor sensitization, revealing that this region may be associated with this enduring behavioral phenotype initiated by methamphetamine. The present findings expand our understanding of the neuroanatomical and molecular substrates that may play a role in the persistence of druginduced sensitization.

Animals↗

PubMed1998

Disturbance of consciousness due to methamphetamine abuse. A study of 2 patients.

The present paper reports 2 cases of methamphetamine abuse. Following consecutive methamphetamine administration, the patients developed acute intoxication, during which time they showed a unique type of disturbance of consciousness: delirium and twilight state. In both cases, mental status changed, passing through three distinct stages: restlessness and insomnia, hallucinatory paranoid state, and disturbance of consciousness. A review of the literature suggests that disturbance of consciousness may occur occasionally during the course of amphetamine and methamphetamine intoxication, although these symptoms can be overlooked easily due to confounding symptomatology.

Central Nervous System Stimulants↗

PubMed2006

Methamphetamine use, self-reported violent crime, and recidivism among offenders in California who abuse substances.

This study uses data from 641 state prison parolees in California to examine the associations between methamphetamine use and three measures of criminal behavior: (a) self-reported violent criminal behavior, (b) return to prison for a violent offense, and (c) return to prison for any reason during the first 12 months of parole. Methamphetamine use was significantly predictive of self-reported violent criminal behavior and general recidivism (i.e., a return to custody for any reason). However, methamphetamine use was not significantly predictive of being returned to custody for a violent offense. These trends remained even after controlling for involvement in the drug trade (i.e., sales, distribution, or manufacturing).

Adult↗

PubMed2004

A polymorphism of DRD2 gene and brain atrophy in methamphetamine psychosis.

Our group, Ujike et al., recently reported that the A1 allele of TaqI A polymorphism of the dopamine receptor D2 (DRD2) gene, associated with transient psychosis, significantly differs from that of patients with prolonged psychosis in methamphetamine psychosis. Therefore, we examined the association between the TaqI A polymorphism of the DRD2 gene and the brain MRI view for patients with methamphetamine psychosis. The subjects underwent brain MRI scans using the FLAIR method. Genotyping was performed by PCR-RFLP methods using genomic DNA extracted from peripheral blood by the phenol method. Ten subjects had the A1/A2 genotype, eleven subjects had the A2/A2 genotype, and no subject had the A1/A1 genotype. The domain size, including the thalamus and basal ganglia that were inside each side of the putamens, did not differ between the three groups (the A1/A2-group, the A2/A2-group, and the young healthy person group). In the comparison based on this domain, the temporal lobe tended to narrow in the A2/A2-group compared to the A1/A2-group (P = .06). The other domain (cerebrum, corpus callosum, etc.) showed no difference between the A1/A2-group and the A2/A2-group. It is suggested that in methamphetamine psychosis the TaqI A polymorphism not only regulates prolongation of psychosis symptoms but also influences the form of the temporal lobe.

Adult↗

PubMed2004

Clinical features of nicotine dependence compared with those of alcohol, methamphetamine, and inhalant dependence.

A new clinical evaluation form was developed to compare the clinical features of nicotine dependence with those associated with other abused drugs. A new scoring system for clinical evaluation was developed. The form consisted of five scoring items: subjective effects, liking (of drug), withdrawal syndrome, acute psychic and physical disorders, and social disturbance. A preliminary clinical investigation was performed to test the validity of the evaluation form. Study subjects were those showing dependence on nicotine (cigarette smoking, n = 40), alcohol (n = 39), methamphetamine (n = 31), and inhalants (n = 30), who fulfilled the DSM-IV-TR criteria for drug dependence disregarding the state of "a maladaptive pattern of substance use, leading to clinically significant impairment or distress," and gave written informed consent for participation in the study. Nicotine caused a mild or the least degree of subjective effects, liking, and psychic and physical withdrawal symptoms, without any significant social disturbance or acute disorders. With alcohol, liking, withdrawal syndrome, and acute physical disorders were prominent. Methamphetamine produced the most serious acute psychic disorders, with intensive acute physical disorders and psychic withdrawal symptoms. Inhalants were characterized by an intensive degree of acute psychic disorders. As for social disturbance, alcohol, methamphetamine, and inhalants showed more significant influence than nicotine. Our study findings revealed that the clinical features of drug dependence could be evaluated by using the new clinical evaluation form. Further study is required to clarify the clinical features of nicotine dependence compared with those of other drugs of dependence.

Administration, Inhalation↗