Methamphetamine (meth) as a substance of the amphetamine type acts primarily in the central nervous system (CNS).
It is more lipophilic than its metabolites and can therefore easily cross the blood-brain barrier. The release of catecholamines,
such as epinephrine, dopamine, and serotonin, with concomitant inhibition of their reuptake, is well studied as a major mechanism
of psychoactivity. Characterization of a cohort from the Leipzig Heart Center showed that young patients have cardiac pathologies
after regular use of meth. These pathologies range from hypertension to arrhythmias, vasospasm, cardiomyopathies to accelerated
arteriosclerosis, vascular dissections and sudden cardiac death. Central nervous stimulated catecholamine action is discussed as
the cause of the observed cardiotoxicity, but also direct damage to myocardial or other cells. Whether catecholamines or direct
effects on myocardium and vasculature are the cause of the meth-associated cardiac injury requires further research.
Identification of molecular targets and drug-induced signal transduction is beyond dispute linking their known damaging effects
to subcellular key players following drug - driven alternative signaling. Therefore, adverse effects of meth on endothelial and
cardiac cells are monitored using impedance spectroscopy in real-time. The involvement of proteinkinase C, protein phosphatase 2A,
endothelial NO synthase as well as von Willebrand factor, endothelin and inflammatory signaling are investigated on gene and
protein expression levels.
The understanding of meth-induced intracellular signaling will lead to improved treatment of cardiac events among patients
following meth abuse.
