Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:537-46-2 (Methamphetamine)
2,465 document(s) hit in 27,025,112 MEDLINE articles (0.00 seconds)

Methamphetamine administration reduces hippocampal vesicular monoamine transporter-2 uptake.
Repeated high-dose injections of methamphetamine (METH) rapidly decrease dopamine uptake by the vesicular monoamine transporter-2 (VMAT-2) associated with dopaminergic nerve terminals, as assessed in nonmembrane-associated vesicles purified from striata of treated rats. ...
PMID:16687477 J. Pharmacol. Exp. Ther. 2006 May 10

Methamphetamine-induced locomotor activity and sensitization in dopamine transporter and vesicular monoamine transporter 2 double mutant mice.
The dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2) play pivotal roles in the action of methamphetamine (MAP), including acute locomotor effects and behavioral sensitization. However, the relative impact of heterozygous DAT and VMAT2 knockouts (KOs) on the behavioral effects of MAP remains unknown. To evaluate the roles of DAT and VMAT2 in MAP-induced locomotor behavior, we examined locomotor activity and sensitization in heterozygous DAT KO (DAT+/-), heterozygous VMAT2 KO (VMAT2+/-), double heterozygous DAT/VMAT2 KO (DAT+/-VMAT2+/-), and wild-type (WT) mice. ... Heterozygous deletion of DAT attenuates the locomotor effects of MAP and may play larger role in behavioral responses to MAP compared to heterozygous deletion of VMAT2.
PMID:17377774 Psychopharmacology (Berl.) 2007 Mar 22

Methamphetamine-induced alterations in monoamine transport: implications for neurotoxicity, neuroprotection and treatment.
... The scope of this review includes the English language dopamine transporter and vesicular monoamine transporter-2 primary literature to April 2006 identified by Pubmed, Science Citation Index and SciFinder Scholar literature searches. Changes in the function of the plasmalemmal dopamine transporter and the vesicular monoamine transporter-2 are key components of methamphetamine-induced persistent dopaminergic deficits. ...
PMID:17493052 Addiction 2007 May 12

Approaches to the development of medications for the treatment of methamphetamine dependence.
Methamphetamine abuse has become an increasing problem in both the United States and globally with concomitant increases in adverse medical, social and environmental sequelae. ... Methamphetamine has a rich pharmacology that theoretically provides many opportunities for potential pharmacotherapeutic intervention. ... Scientifically based approaches to medications development by evaluating medications that limit brain exposure to methamphetamine; modulate methamphetamine effects at vesicular monoamine transporter-2 (VMAT-2); or affect dopaminergic, serotonergic, GABAergic, and/or glutamatergic brain pathways that participate in methamphetamine's reinforcing effects are presented. ...
PMID:17493058 Addiction 2007 May 12

Long-term methamphetamine administration in the vervet monkey models aspects of a human exposure: brain neurotoxicity and behavioral profiles.
Methamphetamine (METH)-associated alterations in the human striatal dopamine (DA) system have been identified with positron emission tomography (PET) imaging and post-mortem studies but have not been well correlated with behavioral changes or cumulative METH intake. ... No statistically significant changes were detected for [3H]dihydrotetrabenazine binding to the vesicular monoamine transporter (METH-lower by 10%) or for [3H]SCH 23390 and [3H]raclopride binding to DA D1 and D2 receptors, respectively. ...
PMID:17625500 Neuropsychopharmacology 2007 Jul 11

A rapid oxidation and persistent decrease in the vesicular monoamine transporter 2 after methamphetamine.
Methamphetamine (METH) produces long-term decreases in markers of dopamine (DA) terminals in animals and humans. A decrease in the function of the vesicular monoamine transporter 2 (VMAT2) has been associated with damage to striatal DA terminals caused by METH; however, a possible mechanism for this decrease in VMAT2 function has not been defined. The current study showed that METH caused a rapid decrease to 68% of controls in VMAT2 protein immunoreactivity of the vesicular fraction from striatal synaptosomes within 1 h after a repeated high-dose administration regimen of METH. This decrease was associated with a 75% increase in nitrosylation of VMAT2 protein in the synaptosomal fraction as measured by nitrosocysteine immunoreactivity of VMAT2 protein. The rapid decreases in VMAT2 persisted when evaluated 7 days later and were illustrated by decreases in VMAT2 immunoreactivity and DA content of the vesicular fraction to 34% and 51% of control values, respectively. ... These studies demonstrate that METH causes a rapid neuronal nitric oxide synthase-dependent oxidation of VMAT2 and long-term decreases in VMAT2 protein and function. ...
PMID:17683483 J. Neurochem. 2007 Aug 7

Tamoxifen protects male mice nigrostriatal dopamine against methamphetamine-induced toxicity.
... Methamphetamine reduced striatal dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations, striatal and substantia nigra dopamine and vesicular monoamine transporter specific binding as well substantia nigra dopamine and vesicular monoamine transporter mRNA levels and increased striatal preproenkephalin mRNA levels. ...
PMID:17825264 Biochem. Pharmacol. 2007 Jul 14

Differential regional effects of methamphetamine on dopamine transport.
... This stimulant likewise causes rapid (within 1 h) and persistent (at least 48 h) decreases in activities of striatal: 1) dopamine transporters, as assessed in synaptosomes; and 2) vesicular monoamine transporter -2 (VMAT-2), as assessed in a non-membrane-associated (referred to herein as cytoplasmic) vesicular subcellular fraction. ... Methamphetamine also rapidly and reversibly (within 48 h) decreased cytoplasmic VMAT-2 function in this region, with relatively little effect on cytoplasmic VMAT-2 immunoreactivity. ... Taken together, these data suggest that deficits in plasmalemmal and vesicular monoamine transporter activity lasting greater than 24-48 h may be linked to the long-lasting dopaminergic deficits caused by methamphetamine and appear to be region specific.
PMID:18599036 Eur. J. Pharmacol. 2008 May 28

Protective actions of the vesicular monoamine transporter 2 (VMAT2) in monoaminergic neurons.
... In the case of dopamine, this dual role of VMAT2 is combined-dopamine is more readily oxidized in the cytosol where it can cause oxidative stress so packaging into vesicles serves two purposes: neurotransmission and neuroprotection. Furthermore, the deleterious effects of exogenous toxicants on dopamine neurons, such as MPTP, can be attenuated by VMAT2 activity. ... Methamphetamine interferes with vesicular sequestration and increases the production of dopamine, escalating the amount in the cytosol and leading to oxidative damage of terminal components. Vesicular transport seems to resist this process by sequestering much of the excess dopamine, which is illustrated by the enhanced methamphetamine neurotoxicity in VMAT2-deficient mice. It is increasingly evident that VMAT2 provides neuroprotection from both endogenous and exogenous toxicants and that while VMAT2 has been adapted by eukaryotes for synaptic transmission, it is derived from phylogenetically ancient proteins that originally evolved for the purpose of cellular protection.
PMID:19259829 Mol. Neurobiol. 2009 Mar 4

Detection of methamphetamine neurotoxicity in forensic autopsy cases.
Methamphetamine (METH) is a powerful stimulant drug of abuse with potent addictive and neurotoxic properties. ... The tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) levels and glial reactions in the striata of METH abusers were examined using immunohistochemical technique. ... Although significant differences in VMAT2 levels were not common, the levels of VMAT2--a stable marker of striatal dopaminergic terminal integrity--were remarkably reduced in some METH users. ...
PMID:19269222 Leg Med (Tokyo) 2009 Mar 6


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