A review of neuroprotective agents.

The brain remains an area where little corrective surgery can be performed and the reversal of damage is almost impossible. Recently, reports of agents offering neuroprotection have begun to appear in the literature. The concept of neuroprotection is the administration of some agent, which should reverse some of the damage or prevent further damage. Some agents offer protection against cell degeneration to the neuronal cells. Still other agents specifically protect the dopamine neurons and the retina. The majority of neuroprotective agents are antioxidants. An immunosuppressive calcineurin inhibitor, NOS inhibitor, sigma-1 modulator, AMPA antagonist and Ca2+ channel blocker have all shown neuroprotective activity. An estrogen agonist and two glycoprotein IIb/IIIa antagonists also exhibit neuroprotective activity. Most of the synthetic compounds presented were not originally designed as neuroprotective agents but were found to possess neuroprotective activity in later studies. Many of these compounds are biologically active natural products, either plant extracts or endogenous peptides/proteins. This review will present the most recent reports on these agents.

A review of chemical agents in the pharmacotherapy of addiction.

Chemical substance abuse has tormented mankind throughout history. A number of chemical approaches have been employed in an attempt to treat chemical addiction. Unfortunately, most of these have proven unsuccessful though several chemical entities have been shown to be moderately effective. The naturally occurring alkaloid ibogaine has been reported to interrupt the cravings for alcohol, cocaine and opiates. Other alkaloids from Tabernanthe iboga, such as ibogamine and tabernanthine, provide insight into the structure activity relationship at the different receptors believed to be involved in addiction. The synthetic iboga alkaloid congener, 18-MC, also shows potential as an anti-addictive agent without the hallucinogenic effects of ibogaine. Additionally, acamprosate, BP 897, GBR12909, lofexidine and memantine have shown promising results in the treatment of addiction. All of these leads provide a start for the medicinal chemist to design anti-addictive agents, since currently no drugs are approved in the U.S. for the treatment of addictions to cocaine, methamphetamine, other stimulants or PCP.

A review of cancer chemopreventive agents.

In the late 20(th) century, the treatment of cancer began to include its prevention. Today, compounds exist that will lower the risk of developing certain types of cancer. This has been demonstrated in studies where chemically induced tumor growth has been slowed or reversed. Anti-inflammatory compounds having chemopreventive activity are piroxicam, sulindac, aspirin, celecoxib and curcumin. The selective estrogen receptor modulators, tamoxifen and raloxifene, are beneficial in the prevention of estrogen dependent tumors. Retinoids, vitamin A derivatives, such as targretin and fenretinide are useful in the prevention of tumors. Compounds containing sulfur, such as sulforaphane and oltipraz, are even useful as radioprotective agents. The steroid dehydroepiandosterone can inhibit experimental carcinogenesis. All of these chemical classes provide a start for the medicinal chemist to design more effective chemopreventive agents. The biomarkers used to determine the chemopreventive activity of new compounds are quite often activities of enzymes. The identification of those individuals at high risk is still in its infancy and presents a troubling dilemma.

Porcelain shoulder adaptation using direct refractory dies.

Eleven direct refractory dies were made from separate polysulfide rubber impressions of two Dentoform teeth which had been prepared for porcelain-fused-to-gold veneer crowns with labial porcelain shoulders. Porcelain veneer crowns were built and fired directly on the dies, following the manufacturer's instructions and using a common laboratory technique. The finished crowns were seated on the Dentoform teeth, and the porcelain-tooth adaptation was measured with a micrometer eyepiece in a dissecting microscope. In general, the study indicated that by use of a direct refractory die, the porcelain adaptation of an average porcelain shoulder veneer crown could be made to fall within the tolerances of a clinically acceptable gold margin (39 mu).21 The crown could likewise be made to adapt closer than the normal thickness of cement film may allow (20 to 40 mu).22 However the adaptation of many crowns was more uneven than the above statements would tend to indicate. The study also showed that with great care and a limited number of firings, margins of a lesser thickness than a piece of 0.001 inch (25.4 mu) platinum foil could be attained. There appears to be promise in the use of a direct refractory die material. However, more studies are needed to overcome some of the problems in the technique described.