Chemical Education Today
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Some Food for Thought by Paul F. Schatz mid brain
Very often, while reading information sources—magazines, journals, newspapers, web sites, etc.—I am struck by the number of connections that can be made between the apparently diverse sources. The topics and the associated connections provide interesting starting points for class discussions or research projects. Recently, the topic that caught my attention was brain chemistry. The first article encountered was a brief overview of brain chemistry by Graeme I. Stevenson and Raymond Baker in Education in Chemistry (September 1996, pp 124– 128). The mechanism of neurotransmission is described. Information about the neurotransmitters dopamine, acetylcholine, histamine, and serotonin is presented in tabular form. Included in this data are biological precursors, agonists, and antagonists. The authors then briefly describe the three major disorders of the brain, Parkinson’s disease, depression, and Alzheimer’s disease. These are discussed in the context of neurotransmitters. Symptoms of Parkinson’s disease are rhythmic tremors and stiffness of movement. Other symptoms can include depression and dementia. Typically, the disease strikes late in one’s life, most patients being 60 or older before the onset of the first symptoms. The HO NH2 disorder is associated with a loss of dopamine in the substantia nigra of the brain. HO Treatments for Parkinson’s dopamine disease either try to replace the dopamine ( L -dopa therapy), increase the lifeN+(CH3)3 time of the dopamine at the O synapse (Eldepryl therapy), or stimulate the dopamine O receptors (Parlodel therapy). acetylcholine While most people can have good days and bad days, it is estimated that 5% of the population of the United NH2 N States experience some form of clinical depression. Depression seems to be associN ated with abnormal concenhistamine H trations of the neurotransmitters serotonin and norepiHO nephrine. Treatment for depression has focused on inhibiting the reuptake mechaNH2 nism of the neurotransmitter. The most successful selective serotonin reuptake inhibitor N (SSRI) is Prozac. H Senile dementia has serotonin long been recognized in elderly patients. Although some Chemicals that act as dementia can be attributed neurotransmitters in the to complications from other brain. diseases, such as Parkinson’s,
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it is estimated that 45% of the population substantia nigra over the age of 85 suffer brainstem from a neurodegenerative disease known as Alzheimer’s disease. This disease is characterized by physiological changes in the brain—atrophy (shrinking) of the brain, loss of neurones (specialized neurotransmission cells) and the appearance of plaques on the brain. Biochemically, it is thought to be linked to a decrease in the availability of acetylcholine. Drug therapy with Tacrine (Cognex) inhibits the enzyme acetycholine esterase and thus inNH2 creases the availability of acetylcholine. However, most researchers believe that so far the treatments for Alzheimer’s disease address the symptoms of the N disease and not the root cause of it. The January 1997 issue of Scientific Tacrine is the most American has an informative article dewidely used drug for scribing the latest thinking about the treating Alzheimer’s causes of Parkinson’s disease, “Underdisease. standing Parkinson’s Disease”, by Moussa B. H. Youdim and Peter Riederer. This article describes recent research into the causes of Parkinson’s disease. Although the evidence is not conclusive, it suggests that free radicals cause oxidative damage in the substantia nigra of the brain. This article provides a good review of the history, biology, physiology, and biochemistry of Parkinson’s disease.
N
HO
NH2
CO2H HO
Eldepryl
L -dopa
O
Three drugs that are used to treat Parkinson’s disease.
Journal of Chemical Education • Vol. 74 No. 7 July 1997
H
O
OH
N H
N
H
N
N O
N H
Parlodel Br
Chemical Education Today
Black pepper is the ripened berries of piper nigrum and is the most widely used spice in the world.
In November 1996, the news wires were buzzing with stories of a promising new class of drugs for Alzheimer’s disease called ampakines. The drugs had been developed at the University of California at Irvine and been licensed by Cortex Pharmaceuticals. The lead compound was called CX-516 and tests on laboratory rats demonstrated that older rats given the drug had a dramatically improved ability to find their way out of a maze and to remember the route later. Human trials had just been approved and were scheduled to begin in early 1997. The January 20, 1997, issue of Chemistry and Engineering News (pp 29–35) contains an interesting background article on the development of new drugs for Alzheimer’s disease, including CX-516. Digging into the research literature, it is interesting to note an earlier report of a compound for enhancing memory, 1-(1,3-benzodioxol-5ylcarbonyl)piperidine (U. Staubli, G Rogers, and G. Lynch, Proc. Natl. Acad. Sci. USA, 91, pp 777–781, January 1994). The structural similarities between CX-516 and 1-(1,3benzodioxol-5-ylcarbonyl)piperidine are obvious. However, I am struck by the structural similarities between 1-(1,3benzodioxol-5-ylcarbonyl)piperidine and piperine, the component of black pepper that gives it its hot taste. Vinylogy, the idea that two structures display similar chemical reactivity if they differ only in the number of conjugated double bonds, suggests that piperine and 1-(1,3-benzodioxol-5ylcarbonyl)piperidine should have similar chemical behavior. It makes one wonder if one can enhance one’s memory by eating black pepper. Are there any ethnobotanists out there who have any information on a link between black pepper and memory?
O N N
CX-516 N
O O
N
piperine O
OH HO
NH2
HO
norepinephrine
The similarities in the structures of norepinephrine and Prozac could partially explain the effectiveness of Prozac therapy for depression.
O O
N
O
1-(1,3-benzodixol-5-ylcarbonyl)piperidine
F3C
O
H N
Prozac
The electron potential is mapped onto the surface of uniform electron density for CX-516, piperine, and 1-(1,3-benzodixol-5ylcarbonyl)piperidine. The surfaces are similar except piperine has two double bonds which act as spacers.
Paul F. Schatz is in the Department of Chemistry, University of Wisconsin–Madison, Madison, WI 53706; email:
[email protected].
Vol. 74 No. 7 July 1997 • Journal of Chemical Education
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