Drugs of abuse-induced hyperthermia, blood-brain barrier dysfunction and neurotoxicity: neuroprotective effects of a new antioxidant compound H-290/51

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Drugs of abuse-induced hyperthermia, blood-brain barrier dysfunction and neurotoxicity : neuroprotective effects of a new antioxidant compound H-290/51

Sharma, Hari Shanker (author): Uppsala universitet,Anestesiologi och intensivvård,Anaesthesiology and Intensive Care

Sjöquist, Per-Ove (author): Uppsala universitet,Anestesiologi och intensivvård

Ali, Syed F (author): Uppsala universitet,Anestesiologi och intensivvård

(creator_code:org_t)

Bentham Science Publishers Ltd. 2007
2007
English.
In: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 13:18, s. 1903-1923

Related links:: http://www.ncbi.nlm....; show more...; https://urn.kb.se/re...; https://doi.org/10.2...; show less...

Research review (peer-reviewed)

Abstract Subject headings

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.

Keyword

Amphetamine-Related Disorders/complications/physiopathology
Animals
Antioxidants/*pharmacology/therapeutic use
Blood-Brain Barrier/*drug effects/metabolism/pathology/physiopathology
Central Nervous System Stimulants/adverse effects
Fever/etiology/metabolism/pathology/physiopathology/*prevention & control
Humans
Indoles/*pharmacology/therapeutic use
Methamphetamine/adverse effects
Morphine Dependence/complications/physiopathology
Neurons/drug effects/metabolism
Neuroprotective Agents/*pharmacology/therapeutic use
Neurotoxicity Syndromes/etiology/metabolism/pathology/physiopathology/*prevention & control
Neurotransmitter Agents/metabolism
Oxidative Stress/drug effects
Reactive Oxygen Species/metabolism
Substance Withdrawal Syndrome/metabolism/pathology/physiopathology/*prevention & control
Substance-Related Disorders/*complications/metabolism/pathology/physiopathology
MEDICINE
MEDICIN

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