Abstract
The psychostimulants, morphine and methamphetamine are well known drugs of abuse that induce brain pathology and/or neurodegeneration resulting in a huge burden on our society. The possible mechanisms of psychostimulants induced neuropathology and neurodegeneration are still not well known. The drugs of abuse results in profound hyperthermia and widespread alterations in neurochemical metabolism in the central nervous system (CNS). It appears that psychostimulants induced hyperthermia and/or release of neurochemicals influence the blood-brain barrier (BBB) dysfunction leading to brain pathology. The drugs of abuse also induce oxidative stress resulting in generation of free radicals and lipid peroxidation. Thus, further research is needed to understand the basic function of BBB disruption and temperature regulation by psychostimulants and to modify them pharmacologically to attenuate brain dysfunction and neuropathology. This review is focused on the problems of morphine and methamphetamine induced hyperthermia and their effects on breakdown of the BBB function leading to brain damage. Works done in our laboratory suggest that hyperthermia caused by these drugs is responsible for BBB disruption and neurodegeneration. This hypothesis is further supported by our observation that pretreatment with a portent antioxidant compound H-290/51 attenuates the BBB disruption and induces marked neuroprotection following morphine induced withdrawal and methamphetamine induced neurotoxicity. The possible mechanisms and functional significance of these findings are discussed.
Keywords: Morphine, methamphetamine, drugs of abuse, dependence, withdrawal symptoms, antioxidants, H-290/51, free radical formation, lipid peroxidation, neuroprotection
Current Pharmaceutical Design
Title: Drugs of Abuse-Induced Hyperthermia, Blood-Brain Barrier Dysfunction and Neurotoxicity: Neuroprotective Effects of a New Antioxidant Compound H-290/51
Volume: 13 Issue: 18
Author(s): Hari Shanker Sharma, Per-Ove Sjoquist and Syed F. Ali
Affiliation:
Keywords: Morphine, methamphetamine, drugs of abuse, dependence, withdrawal symptoms, antioxidants, H-290/51, free radical formation, lipid peroxidation, neuroprotection
Abstract: The psychostimulants, morphine and methamphetamine are well known drugs of abuse that induce brain pathology and/or neurodegeneration resulting in a huge burden on our society. The possible mechanisms of psychostimulants induced neuropathology and neurodegeneration are still not well known. The drugs of abuse results in profound hyperthermia and widespread alterations in neurochemical metabolism in the central nervous system (CNS). It appears that psychostimulants induced hyperthermia and/or release of neurochemicals influence the blood-brain barrier (BBB) dysfunction leading to brain pathology. The drugs of abuse also induce oxidative stress resulting in generation of free radicals and lipid peroxidation. Thus, further research is needed to understand the basic function of BBB disruption and temperature regulation by psychostimulants and to modify them pharmacologically to attenuate brain dysfunction and neuropathology. This review is focused on the problems of morphine and methamphetamine induced hyperthermia and their effects on breakdown of the BBB function leading to brain damage. Works done in our laboratory suggest that hyperthermia caused by these drugs is responsible for BBB disruption and neurodegeneration. This hypothesis is further supported by our observation that pretreatment with a portent antioxidant compound H-290/51 attenuates the BBB disruption and induces marked neuroprotection following morphine induced withdrawal and methamphetamine induced neurotoxicity. The possible mechanisms and functional significance of these findings are discussed.
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Cite this article as:
Hari Shanker Sharma , Per-Ove Sjoquist and Syed F. Ali , Drugs of Abuse-Induced Hyperthermia, Blood-Brain Barrier Dysfunction and Neurotoxicity: Neuroprotective Effects of a New Antioxidant Compound H-290/51, Current Pharmaceutical Design 2007; 13 (18) . https://dx.doi.org/10.2174/138161207780858375
DOI https://dx.doi.org/10.2174/138161207780858375 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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