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PubMedDate not supplied

Methamphetamine in antemortem blood and urine by radioimmunoassay and GC/MS.

Methamphetamine abuse is increasing and methamphetamine is second only to alcohol as a positive finding in cases submitted to the San Diego Sheriff's Crime Laboratory. In general, whole blood specimens are submitted more often than urine. A modified version of a commercially available radioimmunoassay, Coat-A-Count (CAC) Methamphetamine, was investigated as a screen for methamphetamine in whole blood and urine. The assay was modified by using 100 microL of sample, making up standards in whole beef blood, extending the incubation time to 2 h or overnight, and using a cutoff reference of 50 ng/mL methamphetamine. The detection limit for the CAC Methamphetamine kit was 20 ng/mL methamphetamine in whole blood. The CAC Methamphetamine results were compared to Abuscreen Amphetamine High Specificity results and to gas chromatography/mass spectrometry (GC/MS) quantitation of amphetamine and methamphetamine for 157 positive and 48 negative blood specimens. With the CAC Methamphetamine assay there were 2 false negatives detected, both less than the 50 ng/mL cutoff level. There were 12 (6%) false positives with the CAC Methamphetamine assay and 29 (14%) false positives with the Abuscreen Amphetamine assay. Of the positive samples, 95% contained only methamphetamine, with an average concentration of 308 ng/mL, range 25-2030 ng/mL.

Evaluation Studies as Topic↗

PubMed2005

Methamphetamine-using HIV-positive men who have sex with men: correlates of polydrug use.

Methamphetamine use has become a major problem among communities of men having sex with men (MSM), where it has been associated with high-risk behaviors. Methamphetamine is often combined with other drugs that may increase its risks and adverse health consequences. To examine differences in background characteristics, HIVrisk behaviors, and psychosocial variables among polydrug-using HIV-positive MSM, the researchers classified a sample of 261 HIV-positive, methamphetamine-using MSM into three user groups: (1) methamphetamine only; (2) methamphetamine, marijuana, and poppers (light polydrug users); and (3) methamphetamine and other drugs (e.g., cocaine, heroin, hallucinogens, and ketamine; heavy polydrug users). Only 5% reported using only methamphetamine during the past 2 months; 31% were classified as light polydrug users, and 64% were classified as heavy polydrug users. Heavy polydrug users were significantly younger than light polydrug users (35.6 vs. 38.4, P<.01) and reported using methamphetamine for significantly fewer years (10.3 vs. 14.2 years, P<.001), but did not differ in the amount and frequency of methamphetamine or alcohol consumed. Heavy polydrug users reported significantly more sex partners of HIV-negative and unknown serostatus and had more unprotected sex with these partners. Heavy polydrug users had significantly higher scores on impulsivity and negative self-perceptions, as compared with those of light polydrug users. In this sample of HIV-positive MSM, most of those who used methamphetamine had a pattern of polydrug use. Heavy polydrug users reported significantly more high-risk sexual behaviors and tended toward higher levels of impulsivity than light polydrug users. The implications of these findings are two-fold: (1) Longitudinal research is needed to establish causal relationships among methamphetamine use, impulsivity, negative self-perceptions, and sexual risk behavior in this target population; (2) behavioral interventions should evaluate whether methamphetamine use and sexual risk behavior can be reduced by modifying impulsivity and negative self-perceptions.

Adult↗

PubMed2004

Effects of dopamine- and serotonin-related compounds on methamphetamine-induced self-injurious behavior in mice.

Methamphetamine induces hyperlocomotion, and high doses of methamphetamine induce self-injurious behavior (SIB) in rodents. It is well known that the monoaminergic system is involved in methamphetamine-induced behavior. However, the effects of dopamine- and serotonin (5-HT)-related compounds on high-dose methamphetamine-induced behavior have not been sufficiently clarified. Therefore, the present study was designed to investigate the effects of dopamine receptor antagonists and indirect 5-HT receptor agonists on high-dose methamphetamine-induced behavior in mice. Methamphetamine (20 mg/kg) initially increased locomotor activity. As the dosage increased, continuous SIB accompanied by a reduction in locomotor activity was observed. The hyperlocomotion and SIB induced by 20 mg/kg of methamphetamine was abolished by high doses of SCH23390 and haloperidol, indicating that the hyperlocomotion and SIB induced by high doses of methamphetamine are mediated by the activation of D1- and D2-receptors. Furthermore, haloperidol (0.1 mg/kg) potently increased locomotor activity in combination with 20 mg/kg methamphetamine. These results suggest that excess dopaminergic activation, especially activation of dopamine D2-receptors, may be involved in the decrease in locomotor activity induced by a high dose of methamphetamine. On the other hand, indirect 5-HT receptor agonists attenuated methamphetamine-induced SIB, suggesting that the stimulation of 5-HT receptors plays an important role in high-dose methamphetamine-induced SIB in mice.

Animals↗

PubMed1999

Behavioral, toxic, and neurochemical effects of sydnocarb, a novel psychomotor stimulant: comparisons with methamphetamine.

Sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine) is a psychostimulant in clinical practice in Russia as a primary and adjunct therapy for a host of psychiatric disorders, including schizophrenia and depression. It has been described as a stimulant with an addiction liability and toxicity less than that of amphetamines. The present study undertook to evaluate the psychomotor stimulant effects of sydnocarb in comparison to those of methamphetamine. Sydnocarb increased locomotor activity of mice with reduced potency (approximately 10-fold) and efficacy compared with methamphetamine. Sydnocarb blocked the locomotor depressant effects of haloperidol at doses that were inactive when given alone. The locomotor stimulant effects of both methamphetamine and sydnocarb were dose-dependently blocked by the dopamine D1 and D2 antagonists SCH 39166 and spiperone, respectively; blockade generally occurred at doses of the antagonists that did not depress locomotor activity when given alone. In mice trained to discriminate methamphetamine from saline, sydnocarb fully substituted for methamphetamine with a 9-fold lower potency. When substituted for methamphetamine under self-administration experiments in rats, 10-fold higher concentrations of sydnocarb maintained responding by its i.v. presentation. Sydnocarb engendered stereotypy in high doses with approximately a 2-fold lower potency than methamphetamine. However, sydnocarb was much less efficacious than methamphetamine in inducing stereotyped behavior. Both sydnocarb and methamphetamine increased dialysate levels of dopamine in mouse striatum; however, the potency and efficacy of sydnocarb was less than methamphetamine. The convulsive effects of cocaine were significantly enhanced by the coadministration of nontoxic doses of methamphetamine but not of sydnocarb. Taken together, the present findings indicate that sydnocarb has psychomotor stimulant effects that are shared by methamphetamine while demonstrating a reduced behavioral toxicity.

Animals↗

PubMed1999

Effects of various serotonin agonists, antagonists, and uptake inhibitors on the discriminative stimulus effects of methamphetamine in rats.

Neurochemical studies indicate that methamphetamine increases central serotonin (5-HT) levels more markedly than other psychomotor stimulants such as amphetamine or cocaine. In the present study, we investigated 5-HT involvement in the discriminative stimulus effects of methamphetamine. In Sprague-Dawley rats trained to discriminate 1.0 mg/kg methamphetamine i.p. from saline under a fixed-ratio schedule of food presentation, the effects of selected 5-HT agonists, antagonists, and uptake inhibitors were tested. Fluoxetine (1.8-18.0 mg/kg) and clomipramine (3.0-18.0 mg/kg), selective serotonin uptake inhibitors, did not produce any methamphetamine-like discriminative stimulus effects when administered alone, but fluoxetine (5.6 mg/kg), unlike clomipramine (5.6 mg/kg), significantly shifted the methamphetamine dose-response curve to the left. Both 8-hydroxy-2-dipropylaminotetralin (0.03-0.56 mg/kg), a full agonist, and buspirone (1.0-10.0 mg/kg), a partial agonist at 5-HT(1A) receptors, partially generalized to the training dose of methamphetamine but only at high doses that decreased response rate. This generalization was antagonized by the coadministration of the 5-HT(1A) antagonist WAY-100635 (1.0 mg/kg). WAY-100635 (1.0 mg/kg) also partially reversed the leftward shift of the methamphetamine dose-response curve produced by fluoxetine. (+/-)-1-(2, 5-Dimethoxy-4-iodophenyl)-2-aminopropane (0.3 mg/kg), a 5-HT(2A/2C) agonist, shifted the methamphetamine dose-response curve to the left, and this leftward shift was antagonized by the coadministration of ketanserin (3.0 mg/kg), a 5-HT(2A/2C) antagonist. Ketanserin (3.0 mg/kg) also produced a shift to the right in the methamphetamine dose-response curve and completely reversed the leftward shift in the methamphetamine dose-response curve produced by fluoxetine. In contrast, tropisetron (1.0 mg/kg), a 5-HT(3) antagonist, produced a shift to the left of the methamphetamine dose-response curve, and this effect of tropisetron was antagonized by the coadministration of m-chlorophenyl-biguanide (1.8 mg/kg), a 5-HT(3) agonist. The present data suggest that the 5-HT system plays a modulatory role in the discriminative stimulus effects of methamphetamine. These effects appear to be mediated through 5-HT release and blockade of reuptake and subsequent activation of 5-HT(2A/2C) receptors, with limited involvement of other 5-HT receptor subtypes.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2005

Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d-methamphetamine's subjective and reinforcing effects.

In healthy human volunteers, we have previously shown that isradipine, a dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine-induced positive subjective effects associated with its abuse liability, presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present study, we combined acute immediate-release (IR) isradipine with repeated sustained-release (SR) isradipine pretreatment to determine whether isradipine could antagonize methamphetamine's positive subjective and reinforcing effects in methamphetamine-dependent research subjects. We included 18 non-treatment-seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this double-blind, within-subject, cross-over study, which was done in a human laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on three different days after 5 days of double-blind cross-over treatment with either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self-report questionnaires measured drug liking, euphoria, craving, stimulation, and methamphetamine preference. Methamphetamine reinforcement was measured by a behavioural procedure involving choices between methamphetamine and money. For those who received isradipine second and placebo first as the pretreatment paradigm but not vice versa, methamphetamine-induced drug liking, elation, and preference were reduced significantly by isradipine. Depending upon conditioning status, isradipine can reduce some methamphetamine-induced positive subjective and reinforcing effects associated with its abuse liability in methamphetamine addicts.

Adolescent↗

PubMed1988

Enhancement of dopamine release from striatal slices of rats that were subchronically treated with methamphetamine.

The effect of dopamine (DA) uptake inhibitors (methamphetamine, nomifensine, and phenylethylamine) on the release of endogenous DA from striatal slices of rats pretreated with methamphetamine (6 mg/kg/day for 9 days) was investigated. The exposure of methamphetamine-pretreated rat striatal slices to a low concentration (10(-7) M, 5 X 10(-7) M) of methamphetamine caused a greater increase in DA efflux than that of saline-treated rat striatal slices. The drug-treated rats displayed an enhanced stereotyped behavioral response to a small dose of methamphetamine (1 mg/kg). Removal of Ca2+ from the superfusion medium did not affect the difference in the rates of methamphetamine (10(-7) M) induced DA release between methamphetamine-treated and saline-treated rat striatal slices. Nomifensine- and phenylethylamine-induced DA release from striatal slices was also enhanced by repeated administration of methamphetamine. On the other hand, there was no difference in K+-induced DA release between the two groups. Moreover, repeated administration of methamphetamine caused a significant increase in 3H-dopamine uptake in rat striatal synaptosomes. These results suggest that the behavioral sensitization produced by the repeated administration of methamphetamine is accompanied by an enhancement in the release of DA induced by methamphetamine, nomifensine, and phenylethylamine in vitro and is also accompanied by increased DA uptake into striatal synaptosomes.

Animals↗

PubMed1985

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.

Amphetamine↗

PubMed1996

Mechanisms for tolerance to methamphetamine effects.

Pretreatment with incremental increases in methamphetamine causes tolerance to serotonergic effects caused by challenging with multiple high doses of methamphetamine (11.5 mg/kg/dose). The brain concentration of methamphetamine following this challenge was reduced in tolerant rats, yet the plasma concentration was elevated. The tolerance was selective for methamphetamine and did not occur when cocaine was used in the pretreatment. The possibility that tolerance affects the distribution of methamphetamine in or out of the brain through an active transport system was examined by combining the transport-blocking drug, probenecid, with a low dose of methamphetamine. The presence of probenecid enhanced methamphetamine-induced serotonergic changes in the hippocampus. The brain concentration of methamphetamine increased in the presence of probenecid; however, a similar increase in the plasma methamphetamine concentration suggests that the effects of probenecid on methamphetamine distribution are not related to the redistribution of methamphetamine that occurs in tolerant animals.

Animals↗

PubMed2003

The bioavailability of intranasal and smoked methamphetamine.

BACKGROUND: Patients in harm-reduction treatment programs are switching from intravenous to other routes of methamphetamine (INN, metamfetamine) administration to avoid risks associated with needle use. Relatively little has been reported about the bioavailability of methamphetamine when smoked or used intranasally. METHODS: Eight experienced methamphetamine users were administered smoked or intranasal methamphetamine concurrently with an intravenous dose of deuterium-labeled methamphetamine. Plasma and urine concentrations were measured for calculation of bioavailability and other pharmacokinetic parameters by noncompartmental methods. RESULTS: Methamphetamine was well absorbed after smoking or intranasal administration, with bioavailabilities of 79% after intranasal administration and 67% of the estimated delivered dose or 37.4% of the absolute (pipe) dose after smoking. Maximum methamphetamine concentrations occurred at 2.7 and 2.5 hours after intranasal and smoked doses. The elimination half-life was similar for intravenous (11.4 hours), intranasal (10.7 hours), and smoked (10.7 hours) methamphetamine. Clearance (272 mL x h(-1) x kg(-1)), steady-state volume of distribution (4.2 L/kg), and mean residence time (16 hours) of the intravenous dose were similar to previously reported values. Dextroamphetamine (INN, dexamfetamine) half-life (all routes) was 16.2 hours. Methamphetamine and dextroamphetamine renal clearances (all routes) were about 100 and 1100 mL x h(-1) x kg(-1), respectively. CONCLUSIONS: Intranasal and smoked methamphetamine are well absorbed. Although intranasal or smoked routes may decrease the risk of transmission of blood-borne diseases, exposure to methamphetamine and the possibility of drug-related complications remain substantial.

Administration, Inhalation↗

PubMed2005

Methamphetamine in hair and interpretation of forensic findings in a fatal case.

Hair analysis for drugs has been developing and is considered a significant tool for distinguishing between recent and long-term drug abuse in forensic and clinical toxicology. Chronic consumption of drugs can gradually induce certain harmful effects on the human organism and can exacerbate some pre-existing diseases. Analysis for drugs in blood or urine in isolation does not provide sufficient information about the history of drug-use by a person and their results cannot be correlated directly with the toxic effects displayed. The chronic abuse of methamphetamine is known to be associated with cardiovascular diseases. During or after autopsy certain types of morphologic alterations are found in the hearts of stimulant addicts. The rapid increase in blood pressure after an intravenous methamphetamine dose can be risky for addicts with arteriosclerosis. However, the anamnestic data about a deceased person may not always be available to explain the pathological findings and to classify the cause of death correctly. The aim of this study was to demonstrate the value of hair analysis for drugs in the context of explaining pathological cardiovascular alterations observed during the autopsy in a case where methamphetamine consumption was involved. In this case, only methamphetamine and metabolites were detected with traces of ephedrine. Ephedrine is the precursor chemical in the illicit synthesis of methamphetamine (known in the Czech Republic as "Pervitin"). The femoral blood level of methamphetamine was 1500 ng/ml. It was documented by a witness that the 31-year-old man died within 1h after an intravenous injection of the drug. The cause of death was established as cerebral edema due to cerebellar bleeding shortly after an intravenous dose of methamphetamine. Findings of methamphetamine in the first three 2-cm hair segments (numbered from the roots) were nearly equal (132+/-9 ng/mg). In the fourth 2-cm segment, it was approximately one-half of previous values. In the remaining, distal 7-cm hair segment sample, the value of methamphetamine was higher and comparable to the third segment. These results provide clear evidence that the man had been a chronic methamphetamine abuser for more than 8 months. This information can help to explain the pathology, the consequence of which could be the bleeding into the cerebellum after the last single methamphetamine dose.

Adult↗

PubMed2006

A comprehensive assessment of the safety of intravenous methamphetamine administration during treatment with selegiline.

Selegiline (L-deprenyl) is a selective irreversible monoamine oxidase B inhibitor shown to be effective in the treatment of Parkinson's and Alzheimer's diseases. Recent evidence suggests that selegiline may also be useful in treating specific aspects of cocaine and nicotine dependence, generating interest in this compound for the treatment of methamphetamine addiction. To investigate this, we performed a randomized, single-blind, placebo-controlled study to evaluate the safety of selegiline treatment (as compared to placebo), concurrent with intravenous methamphetamine (15 or 30 mg). Secondary study objectives included determinations of plasma levels of selegiline and its metabolites, evaluating whether selegiline administration altered the pharmacokinetics of methamphetamine or its metabolites, and evaluating whether selegiline treatment alters the subjective responses to methamphetamine. Twenty-four methamphetamine-dependent participants were randomized to treatment, and 9 of these (N = 5 selegiline, N = 4 placebo) completed the entire protocol. The principal finding from this study was that intravenous administration of moderate doses of methamphetamine was safely tolerated during treatment with selegiline. No participants had electrocardiogram changes, and there were no meaningful differences in any laboratory values either between groups at screening or as a result of the study procedures. In general, adverse events were mild or moderate, and no subjects were discontinued due to adverse events or serious adverse events. Selegiline treatment did not enhance any of the cardiovascular changes (heart rate, blood pressure) produced by methamphetamine administration. Selegiline treatment slightly increased methamphetamine associated "bad effects" but did not alter any other subjective effects. The elimination half-life of methamphetamine was approximately 12 h, and selegiline did not alter clearance of methamphetamine. The available data suggest that selegiline is likely to be safe if used as a pharmacotherapy for methamphetamine dependence.

Adult↗

PubMed1997

The role of delta-opioid receptors in the discriminative stimulus properties of a low dose of methamphetamine.

The effects of selective mu-, delta- and kappa-opioid receptor agonists and antagonists on the discriminative stimulus properties of methamphetamine were examined in rats that had been trained to discriminate between methamphetamine (0.4 mg/kg) and saline. Methamphetamine produced a dose-related increase in methamphetamine-appropriate responses in all of the rats. In generalization tests, neither morphine (a mu-opioid receptor agonist: 0.3-10 mg/kg) nor 3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexo]benzeneacetamide (U50,488H: a kappa-opioid receptor agonist: 1.0-8.0 mg/kg) generalized to the discriminative stimulus properties of methamphetamine. A newly synthesized non-peptide selective delta-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha- octahydroquinolino(2,3,3,-g)isoquinoline (TAN-67: 32 mg/kg) partially generalized (70% methamphetamine-appropriate responses) to the discriminative stimulus properties of methamphetamine. In combination tests, pretreatment with the mu- and kappa-opioid receptor antagonists, beta-funaltrexamine (9.0 mg/kg) and nor-binaltorphimine (10 mg/kg), respectively, had little or no influence on the discriminative stimulus properties of methamphetamine. In contrast, pretreatment with naltrindole (a non-selective delta-opioid receptor antagonist: 3.0 mg/kg) or naltriben (a selective delta2-opioid receptor antagonist: 1.0 mg/kg), but not with 7-benzylidenenaltrexone (a selective delta1-opioid receptor antagonist: 0.5 and 1.0 mg/kg), significantly attenuated the discriminative stimulus properties of methamphetamine. However, naltrindole (3.0 mg/kg) did not significantly attenuate the discriminative stimulus properties of methamphetamine at a higher training dose (1.0 mg/kg). Our findings may have some bearing on the relative importance of the role of delta-opioid (especially delta2-opioid) receptors in the discriminative stimulus properties of a low dose of methamphetamine.

Animals↗

PubMed2001

Differential effects of cocaine and methamphetamine on neurotensin/neuromedin N and preprotachykinin messenger RNA expression in unique regions of the striatum.

This study employed in situ hybridization to directly compare the effects of cocaine and methamphetamine on neurotensin/neuromedin N and preprotachykinin messenger RNAs in distinct striatal regions. Male, Sprague-Dawley rats received a single administration of 15mg/kg methamphetamine (s.c.) or 30mg/kg cocaine (i.p.) and were killed 30min or 3h later. Methamphetamine and cocaine produced significant increases in preprotachykinin messenger RNA in the striatum after 3h, but often in different subregions. Both drugs produced similar effects on preprotachykinin messenger RNA in the rostral striatum. However, methamphetamine produced significant increases in all regions of the caudal striatum, whereas cocaine-induced preprotachykinin messenger RNA expression was limited to dorsal regions of this striatal area. Methamphetamine also produced a significant increase in preprotachykinin messenger RNA in the caudal striatum after 30min, whereas cocaine had no significant effect on preprotachykinin messenger RNA at this early time-point. The pattern of changes in neurotensin/neuromedin N messenger RNA caused by methamphetamine and cocaine after 3h was even more distinct. Cocaine produced significant increases in neurotensin/neuromedin N messenger RNA in all regions of the rostral striatum, whereas methamphetamine had no effect in these areas. Furthermore, in more caudal sections, cocaine predominantly affected neurotensin/neuromedin N expression in dorsal aspects of the striatum, whereas methamphetamine significantly increased neurotensin/neuromedin N messenger RNA in all regions. There was much less effect of either drug on neuropeptide expression in the nucleus accumbens. The only significant effect was an increase in neurotensin/neuromedin N messenger RNA in the core region 3h after methamphetamine administration. These results indicate that methamphetamine and cocaine increase preprotachykinin and neurotensin/neuromedin N messenger RNAs in distinct regions of the striatum. The ability of methamphetamine and cocaine to alter neuropeptide messenger RNA expression in unique regions of the striatum may be important for the long-term effects of these drugs, such as sensitization, since the striatum is not homogeneous in its connections and function.

Animals↗

PubMed2001

Tamoxifen abolishes estrogen's neuroprotective effect upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system.

The effects of 17beta-estradiol and the anti-estrogen, tamoxifen, on methamphetamine-induced neurotoxicity of the nigrostriatal dopaminergic system were examined in ovariectomized CD-1 mice. In Experiment 1, striatal dopamine concentrations from estrogen treated mice were significantly greater than that from non-estrogen treated mice following methamphetamine. Dopamine concentrations from estrogen+tamoxifen+methamphetamine treated mice were decreased compared to estrogen+methamphetamine treated mice and not significantly different from those of tamoxifen+methamphetamine treated mice or mice receiving methamphetamine alone. These results suggest that estrogen is functioning as a neuroprotectant of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity and that this neuroprotective effect of estrogen is abolished in the presence of tamoxifen. In Experiment 2, estrogen administration after methamphetamine treatment did not produce any significant changes in dopamine concentrations compared with methamphetamine treatment alone. The data from Experiment 2 show that estrogen cannot reverse the methamphetamine-induced neurotoxicity upon the nigrostriatal dopaminergic system. Similar results were observed for the potassium-stimulated dopamine outputs from these treatment conditions as evaluated with in vitro superfusion, although a difference between the two measures for the estrogen+methamphetamine treated group was obtained in Experiment 1. These results have important implications for estrogen-tamoxifen interactions upon the nigrostriatal dopaminergic system and the gender differences which are observed in Parkinson's disease and animal models of nigrostriatal dopaminergic neurotoxicity as well as for the proposed use of tamoxifen in pre-menopausal women at risk for breast cancer.

Animals↗

PubMed1999

Methamphetamine use and sexual and injection risk behaviors among out-of-treatment injection drug users.

Our primary objective was to examine the relationship between methamphetamine use and sexual risk-taking behaviors--number of sexual partners, frequency of sexual behaviors with regular and casual partners, trading money or drugs for sex, and condom use--among male and female out-of-treatment injection drug users (OTIDUs). As a risk group for human immunodeficiency virus (HIV) transmission, we also investigated injection behaviors by methamphetamine use. Data were collected from 1392 OTIDUs within the California counties of Fresno, Sacramento, and San Diego. Excluded from this cross-sectional survey were male OTIDUs engaging in sex with only or mostly men since 1978. In bivariate analyses, we found that male OTIDUs with a history of methamphetamine use had more sex partners and participated in more acts of anal insertive intercourse with casual partners and vaginal intercourse with regular and casual partners than male OTIDUs never using methamphetamines. In addition, a greater percentage of male OTIDUs using methamphetamines reported trading sex for money or drugs. Methamphetamine-using female OTIDUs participated in more acts of vaginal intercourse with regular male sex partners than female OTIDUs never using methamphetamines. By multivariate logistic regression, we found methamphetamine use related to consistent condom use among male OTIDUs and among male sex partners of female OTIDUs. Discriminant function analyses revealed that sexual risk taking could be differentiated by methamphetamine use among male OTIDUs. Methamphetamine use also correlated with using shared needles or syringes among male and female OTIDUs and was related to not always disinfecting used needles or syringes with bleach. Our findings suggest that methamphetamines may contribute to heterosexual HIV transmission.

Adolescent↗

PubMed1998

A rapid novel derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography electron ionization and chemical ionization mass spectrometric analysis.

Amphetamine and methamphetamine are commonly abused central nervous system stimulants. We describe a rapid new derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography-mass spectrometric analysis. Amphetamine and methamphetamine, along with N-propyl amphetamine (internal standard), were extracted from urine using 1-chlorobutane. The derivatization with 2,2,2-trichloroethyl chloroformate can be achieved at room temperature in 10 minutes. The electron ionization mass spectrum of amphetamine 2,2,2-trichloroethyl carbamate showed two weak molecular ions at m/z 309 and 311, but showed diagnostic strong peaks at m/z 218, 220, and 222. In contrast, chemical ionization of the mass spectrum of amphetamine 2,2,2-trichloroethyl carbamate showed strong (M + 1) ions at m/z 310 and 312 and other strong diagnostic peaks at m/z 274 and 276. The major advantages of this derivative are the presence of a diagnostic cluster of peaks due to the isotopic effect of three chlorine atoms (isotopes 35 and 37) in the derivatized molecule and the relative ease of its preparation. We also observed strong molecular ions for derivatized methamphetamine in the chemical ionization mass spectrum, but the molecular ions were very weak in the electron ionization mass spectrum. We used the scan mode of mass spectrometry in all analyses. When using a urine standard containing 1,000 ng/mL of amphetamine (a 7.4-micromol/L concentration) and methamphetamine (a 6.7-micromol/L concentration), the within-run precisions were 4.8% for amphetamine and 3.6% for methamphetamine. The corresponding between-run precisions were 5.3% for amphetamine and 6.7% for methamphetamine. The assay was linear for amphetamine and methamphetamine concentrations of 250 to 5,000 ng/mL (amphetamine, 1.9-37.0 micromol/L; methamphetamine, 1.7-33.6 micromol/L). The detection limit was 100 ng/mL (amphetamine, 0.74 micromol/L; methamphetamine, 0.67 micromol/L) using the scan mode of electron ionization mass spectrometry. We observed good a correlation between the concentrations of amphetamine and methamphetamine in five urine specimens positive for amphetamines using the more conventional pentafluoropropionyl derivative and our new derivative using 2,2,2-trichloroethyl chloroformate.

Amphetamine↗

PubMed1996

Effects of sulpiride and nemonapride, benzamide derivatives having distinct potencies of antagonistic action on dopamine D2 receptors, on sensitization to methamphetamine in mice.

The acute ambulatory stimulation by methamphetamine (2 mg kg-1 S.C.) was dose-dependently reduced by 3-h pretreatment or combined treatment with sulpiride (1-100 mg kg-1 S.C.), and combined treatment with nemonapride (0.003-0.03 mg kg-1 S.C.), benzamide derivatives having selective antagonistic action on dopamine D2 receptors. The repeated (5 times) administrations of methamphetamine at 3-day intervals induced a sensitization to its ambulation-increasing effect, and the sensitization was significantly inhibited by 3-h pretreatment with either sulpiride (10-100 mg kg-1), or combined treatment with either sulpiride (3 or 10 mg kg-1) or nemonapride (0.01 or 0.03 mg kg-1) at each methamphetamine administration. Although the ambulation-increasing effect of methamphetamine disappeared by 3 h after the administration, the 3-h post-treatment with sulpiride (3 mg kg-1) or nemonapride (0.03 mg kg-1) after each methamphetamine administration was effective for a significant inhibition of the induction of methamphetamine sensitization, whereas, the comparatively higher doses of sulpiride (30 and 100 mg kg-1 in the combined treatment, and 10-100 mg kg-1 in the post-treatment) did not inhibit the methamphetamine sensitization. On the other hand, the repeated administrations of sulpiride (30 and 100 mg kg-1) alone, but not any doses of nemonapride, at 3-day intervals elicited a significant increase in the sensitivity to methamphetamine. These results suggest that, although the potencies of the anti-methamphetamine effects of sulpiride and nemonapride differ by a factor of 3000, they inhibit the induction of sensitization to methamphetamine in the pretreatment, combined treatment and early post-treatment schedules. However, it is also suggested that the repeated treatment with comparatively higher doses of sulpiride may produce a denervation supersensitivity of dopamine D2 receptors, and resultant increase in the sensitivity to methamphetamine.

Animals↗