Chemicals that act as neurotransmitters in the brain.

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 disorder is associated with a loss of dopamine in the substantia nigra of the brain. Treatments for Parkinson's disease either try to replace the dopamine (l-dopa therapy), increase the lifetime of the dopamine at the synapse (Eldepryl therapy), or stimulate the dopamine receptors (Parlodel therapy).

While most people can have good days and bad days, it is estimated that 5% of the population of the United States experience some form of clinical depression. Depression seems to be associated with abnormal concentrations of the neurotransmitters serotonin and norepinephrine. Treatment for depression has focused on inhibiting the reuptake mechanism of the neurotransmitter. The most successful selective serotonin reuptake inhibitor (SSRI) is Prozac.

The similarities in the structures of norepinephrine and Prozac could partially explain the effectiveness of Prozac therapy for depression.

Senile dementia has long been recognized in elderly patients. Although some dementia can be attributed to complications from other diseases, such as Parkinson's,it is estimated that 45% of the population over the age of 85 suffer from a neurodegenerative disease known as Alzheimer's disease. This disease is characterized by physiological changes in the brainatrophy (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 increases the availability of acetylcholine. However, most researchers believe that so far the treatments for Alzheimer's disease address the symptoms of the disease and not the root cause of it.

Tacrine is the most widely used drug for treating Alzheimer's disease.

Three drugs that are used to treat Parkinson's disease.

The January 1997 issue of Scientific American has an informative article describing the latest thinking about the causes of Parkinson's disease, "Understanding 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.

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-5-ylcarbonyl)piperidine (U. Staubli, G Rogers, and G. Lynch, Proc. Natl. Acad. Sci. USA, 91, pp 777-781, January 1994).

Black pepper is the ripened berries of piper nigrum and is the most widely used spice in the world.

The structural similarities between CX-516 and 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine are obvious. However, I am struck by the structural similarities between 1-(1,3-benzodioxol-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-5-ylcarbonyl)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?

The electron potential is mapped onto the surface of uniform electron density for CX-516, piperine, and 1-(1,3-benzodixol-5-ylcarbonyl) piperidine. The surfaces are similar except piperine has two double bonds which act as spacers.