Review Methamphetamine-induced neurotoxicity: the road to Parkinson’s disease Bessy Thrash, Kariharan Thiruchelvan, Manuj Ahuja, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran Abstract: Studies have implicated methamphetamine exposure as a contributor to the development of Parkinson’s disease. There is a signifi- cant degree of striatal dopamine depletion produced by methamphetamine, which makes the toxin useful in the creation of an animal model of Parkinson’s disease. Parkinson’s disease is a progressive neurodegenerative disorder associated with selective degenera- tion of nigrostriatal dopaminergic neurons. The immediate need is to understand the substances that increase the risk for this debili- tating disorder as well as these substances’neurodegenerative mechanisms. Currently, various approaches are being taken to develop a novel and cost-effective anti-Parkinson’s drug with minimal adverse effects and the added benefit of a neuroprotective effect to fa- cilitate and improve the care of patients with Parkinson’s disease. Amethamphetamine-treated animal model for Parkinson’s disease can help to further the understanding of the neurodegenerative processes that target the nigrostriatal system. Studies on widely used drugs of abuse, which are also dopaminergic toxicants, may aid in understanding the etiology, pathophysiology and progression of the disease process and increase awareness of the risks involved in such drug abuse. In addition, this review evaluates the possible neuroprotective mechanisms of certain drugs against methamphetamine-induced toxicity. Key words: drug abuse, methamphetamine, neurotoxin, Parkinson disease, neuroprotection Introduction Methamphetamine is a psychostimulant and a com- mon drug of abuse. Recently, increased methampheta- mine use, which leads to dependence or addiction, has become a major health concern worldwide. However, methamphetamine has been used in clinical settings as a treatment for narcolepsy and attention deficit hy- peractivity disorder (ADHD) in children, [85]. For these pathological conditions, it is considered a sec- ond line of treatment that is used when amphetamine and methylphenidate cause severe and numerous ad- verse effects. It is also used for weight loss and to maintain alertness, focus, motivation, and mental clarity for extended periods of time, as well as for rec- reational purposes. Methamphetamine easily crosses the blood-brain barrier, enters the brain and triggers an immediate signaling cascade, which releases mono- amines (dopamine, norepinephrine and serotonin). It can also act as a dopaminergic and adrenergic reup- take inhibitor and, at high concentrations, as a monoamine oxidase inhibitor. The major dopaminergic pathways in the brain are the nigrostriatal, mesolimbic, meso- 966