Current Pharmaceutical Design - Volume 10, Issue 7, 2004

In this issue of Current Pharmaceutical Design, five manuscripts delve deep into the history and present day studies of morphine and related opioids, which have been the cornerstone of pain treatment since ancient history. Sabatowski [1] presents a history of pain treatment, starting from the early day opium use in Sumeria and Egypt, mandrake in the middle ages, and passing via Serturner, who in 1805 described for the fi Read More

Pain is a common experience of mankind. Pain theories and the management of pain have been modified throughout the history of mankind. This article gives a brief review on pain, pain believes and pain management from early magico-demonic and magico-religeous ideas and procedures to more empiric-scientific models; from ancient times and primitive cultures to the 20 th century. Due to new anatomical, physiological and Read More

The thevinols and orvinols derived from thebaine via the thebaine-methylvinyl ketone adduct (thevinone) were thoroughly investigated in the 1960's and 1970's by the Reckitt group. From this work a number of important opioids emerged. Buprenorphine is a m partial agonist, κ / δ-antagonist that is now used primarily in the treatment of heroin abuse and dependence though it was initially launched as an analgesic for the treatmen Read More

The discovery of the selective delta (δ) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, was a major advance in the field of δ-opioid ligands. Much research has been performed to uncover the structure-activity relationships (SAR) of this class of ligands and also to compare the diarylmethylpiperazines with the traditional morphinan-based d opioids. This revie Read More

Mediation of antinociception via opioid receptors located in the periphery is a viable strategy to produce analgesia without the occurrence of side effects associated with stimulation of opioid receptors located in the central nervous system. Peripheral opioid receptors are particularly important in inflammatory pain states and in the responses to pruritogenic stimuli, and have been implicated in the transmission of visceral pain. M Read More

The endogenous opioid system plays a central role in pain. Recent advances have permitted imaging of opioid receptors by PET in human subjects while experiencing pain and detection of changes in receptor occupancy. The ability to perform these types of studies is dependent on the development of opioid tracer ligands labeled with positron emitting isotopes. This article follows the development and radiochemistry of Read More

Maneuvering single gene expression is not only an optimal way to study gene function but also an ambitious goal, which will lead to the treatment of a variety of human diseases whose main pathogenetic event is a genetic alteration. The recent efforts focusing on the genome project have led to array based, high throughput, gene expression analysis techniques that allow the study of complex molecular networks. Combining th Read More

The tragic failure of gene therapy resulted in rolling back the research of gene-based medicine. Because of the poor delivery of gene-based medicines, such as antisense oligonucleotides, ribozyme, triplex, or gene both in vitro and in vivo, further development of gene-based medicines as therapeutic agents have stagnated. Although the delivery system plays a critical role in the overall efficacy of oligonucleotides, inapprop Read More

Antisense oligonucleotides (ODN) technology is one of the most promising therapeutic strategies to prevent the progress of diseases through inhibiting the specific gene expression. They are well established to serve as molecular tools for several biologic applications, from the study of single gene function up to complex target validations. From the theoretical simple action, sequence-specific inhibition of mRNA functions Read More

A current goal in molecular medicine is the development of new strategies for the selective inhibition of cancer-critical genes. Triplex-forming oligonucleotides and peptide nucleic acids bind to the double helix of DNA in a sequence-specific manner and with great affinity. Because of these properties, these molecules have been proposed as anti-gene therapeutic drugs. This review summarizes recent results on the use of oli Read More