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Stroke, with or with no ice? Observations on amphetamine for the management of acute stroke

Journal of Human Hypertension volume 21, pages 594–597 (2007)Cite this article

Known as the club drug and as a robust performance enhancer around the world, amphetamine (alpha-methyl-phenethylamine) is a central nervous system stimulant that has become a mainstream prescription drug to treat narcolepsy and attention-deficit hyperactivity disorder (ADHD). Amphetamine is the parent compound of a broad range of psychoactive derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA) (Ecstasy) and methamphetamine. Originally available as racemic salt sulphate with equal amounts of levo- and dextro-isoform, the current predominant form of the drug is dextroamphetamine sulphate (also called dexamphetamine or D-amphetamine) consisting entirely of the D-isomer. Laboratory evidence indicates that D-amphetamine and L-amphetamine act preferentially on the dopaminergic system and norepinephrinergic, respectively, but the main reinforcing and behavioural-stimulant effects of amphetamine are correlated with enhanced dopaminergic activity, primarily in the mesolimbic dopaminergic system.1

The methylation of amphetamine renders the substance more lipid soluble, thereby facilitating its transport across the blood–brain barrier and enhancing its psychostimulatory effects. Its N-methylated analog methamphetamine, popularly referred to as crystal meth or ice, has been prescribed as the centrally active D-isomer of methamphetamine or D-methamphetamine to control narcolepsy, ADHD, and extreme obesity, whereas the other isoform L-methamphetamine, a potent sympathetic nervous system trigger (i.e., increasing heart rate and blood pressure), is available as an the over-the-counter drug Vicks inhaler for nasal decongestant.

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References

  1. Bonci A, Bernardi G, Grillner P, Mercuri NB . The dopamine-containing neuron: maestro or simple musician in the orchestra of addiction? Trends Pharmacol Sci 2003; 24: 172–177.

    Article  CAS  Google Scholar 

  2. Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ . Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration. Pharmacotherapy. 2006; 26: 1501–1510.

    Article  Google Scholar 

  3. Homsi J, Walsh D, Nelson KA . Psychostimulants in supportive care. Support Care Cancer 2000; 8: 385–397.

    Article  CAS  Google Scholar 

  4. Wagner GJ, Rabkin R . Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial. J Clin Psychiatry. 2000; 61: 436–440.

    Article  CAS  Google Scholar 

  5. Robinson RG, Bloom FE . Pharmacological treatment following experimental cerebral infarction: implications for understanding psychological symptoms of human stroke. Biol Psychiatry 1977; 12: 669–680.

    CAS  PubMed  Google Scholar 

  6. Boyeson MG, Feeney DM . Intraventricular norepinephrine facilitates motor recovery following sensorimotor cortex injury. Pharmacol Biochem Behav 1990; 35: 497–501.

    Article  CAS  Google Scholar 

  7. Crisostomo EA, Duncan PW, Propst M, Dawson DV, Davis JN . Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients. Ann Neurol 1988; 23: 94–97.

    Article  CAS  Google Scholar 

  8. Feeney DM, Gonzalez A, Law WA . Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science 1982; 217: 855–857.

    Article  CAS  Google Scholar 

  9. Hovda DA, Feeney DM . Amphetamine with experience promotes recovery of locomotor function after unilateral frontal cortex injury in the cat. Brain Res 1984; 298: 358–361.

    Article  CAS  Google Scholar 

  10. Goldstein LB, Davis JN . Beam-walking in rats: studies towards developing an animal model of functional recovery after brain injury. J Neurosci Methods 1990; 31: 101–107.

    Article  CAS  Google Scholar 

  11. Dietrich WD, Alonso O, Busto R, Watson BD, Loor Y, Ginsberg MD . Influence of amphetamine treatment on somatosensory function of the normal and infarcted rat brain. Stroke 1990; 21: 147–150.

    Article  Google Scholar 

  12. Walker-Batson D, Smith P, Curtis S, Unwin H, Greenlee R . Amphetamine paired with physical therapy accelerates motor recovery after stroke. Further evidence. Stroke 1995; 26: 2254–2259.

    Article  CAS  Google Scholar 

  13. Unwin H, Walker-Batson D . No side effects after low-dose amphetamine administration in stroke rehabilitation. Stroke 2000; 31: 1788–1789.

    Article  CAS  Google Scholar 

  14. Walker-Batson D, Curtis S, Natarajan R, Ford J, Dronkers N, Salmeron E et al. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke 2001; 32: 2093–2098.

    Article  CAS  Google Scholar 

  15. Breitenstein C, Wailke S, Bushuven S, Kamping S, Zwitserlood P, Ringelstein EB et al. D-amphetamine boosts language learning independent of its cardiovascular and motor arousing effects. Neuropsychopharmacology 2004; 29: 1704–1714.

    Article  CAS  Google Scholar 

  16. Sonde L, Nordstrom M, Nilsson CG, Lokk J, Viitanen M . A double-blind placebo-controlled study of the effects of amphetamine and physiotherapy after stroke. Cerebrovasc Dis 2001; 12: 253–257.

    Article  CAS  Google Scholar 

  17. Sonde L, Lokk J . Effects of amphetamine and/or L-dopa and physiotherapy after stroke – a blinded randomized study. Acta Neurol Scand 2007; 115: 55–59.

    Article  CAS  Google Scholar 

  18. Martinsson L, Wahlgren NG . Safety of dexamphetamine in acute ischemic stroke: a randomized, double-blind, controlled dose-escalation trial. Stroke 2003; 34: 475–481.

    Article  CAS  Google Scholar 

  19. Knecht S, Imai T, Kamping S, Breitenstein C, Henningsen H, Lutkenhoner B et al. D-amphetamine does not improve outcome of somatosensory training. Neurology 2001; 57: 2248–2252.

    Article  CAS  Google Scholar 

  20. Martinsson L, Eksborg S, Wahlgren NG . Intensive early physiotherapy combined with dexamphetamine treatment in severe stroke: a randomized, controlled pilot study. Cerebrovasc Dis 2003; 16: 3338–3345.

    Article  Google Scholar 

  21. Treig T, Werner C, Sachse M, Hesse S . No benefit from D-amphetamine when added to physiotherapy after stroke: a randomized, placebo-controlled study. Clin Rehabil 2003; 17: 590–599.

    Article  Google Scholar 

  22. Gladstone DJ, Danells CJ, Armesto A, McIlroy WE, Staines WR, Graham SJ et al. Subacute Therapy with Amphetamine and Rehabilitation for Stroke Study Investigators. Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke: a randomized, double-blind, placebo-controlled trial. Stroke 2006; 37: 179–185.

    Article  Google Scholar 

  23. Platz T, Kim IH, Engel U, Pinkowski C, Eickhof C, Kutzner M . Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial. Restor Neurol Neurosci 2005; 23: 271–280.

    CAS  PubMed  Google Scholar 

  24. Sprigg N, Willmot MR, Gray LJ, Sunderland A, Pomeroy V, Walker M et al. Amphetamine increases blood pressure and heart rate but has no effect on motor recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled trial (ISRCTN 36285333). J Hum Hypertens 2007 [E-pub ahead of print: 19 April 2007; doi:10.1038/sj.jhh.1002205].

  25. Xu Y, Zhang W, Klaus J, Young J, Koerner I, Sheldahl LC et al. Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection. Proc Natl Acad Sci USA 2006; 103: 14489–14494.

    Article  CAS  Google Scholar 

  26. Wang Y, Hayashi T, Chang CF, Chiang YH, Tsao LI, Su TP et al. Methamphetamine potentiates ischemia/reperfusion insults after transient middle cerebral artery ligation. Stroke 2001; 32: 775–782.

    Article  CAS  Google Scholar 

  27. Stroemer RP, Kent TA, Hulsebosch CE . Enhanced neocortical neural sprouting, synaptogenesis, and behavioral recovery with D-amphetamine therapy after neocortical infarction in rats. Stroke 1998; 29: 2381–2393.

    Article  CAS  Google Scholar 

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  1. Department of Neurology, Medical College of Georgia and Medical Research Service, VA Medical Center, Augusta, GA, USA

    C V Borlongan & D C Hess

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  1. C V Borlongan
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Borlongan, C., Hess, D. Stroke, with or with no ice? Observations on amphetamine for the management of acute stroke. J Hum Hypertens 21, 594–597 (2007). https://doi.org/10.1038/sj.jhh.1002206

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