Current Topics in Medicinal Chemistry - Volume 4, Issue 1, 2004

I wish to take this opportunity at the start of the fourth year of publication for Current Topics in Medicinal Chemistry (CTMC) to consider where the journal has come and is heading in the future. This issue (vol 4 / 1) marks the 33rd since publication began in 2001. There were six issues that year, 12 in 2002, and 14 in 2003. We will have 16 issues in 2004 and, remarkably, many of these have already been received and are in the g Read More

Opioids were among the earliest neuropeptides identified in the nervous system. They are some of the most effective pain-relieving drugs used in the clinical management of pain. In addition to their analgesic effect, opioid peptides also affect a number of physiological functions, including hormone secretion, neurotransmitter release, feeding, gastrointestinal motility, and respiratory activity. Research on opioids has been c Read More

This review gives a historical perspective, summarizing approximately 25 years of research on opioids. The “typical” opioid peptides produced in the brain, “atypical” opioids encrypted in milk protein or hemoglobin sequences, and extremely potent and selective opioids of amphibian origin are described. The main focus is on the structure-activity relationship studies of peptide ligands for three main opioid receptor types (μ, δ, κ) Read More

The search for new peptides to be used as analgesics in place of morphine has been mainly directed to develop peptide analogues or peptidomimetics having higher biological stability and receptor selectivity. Indeed, most of the alkaloid opioid counterindications are due to the scarce stability and the contemporary activation of different receptor types. However, the development of several extremely stable and Read More

There is significant experimental evidence implicating the endogenous opioid system (opioid peptides and opioid receptors) with the processes of reward and reinforcement. Indeed, many behaviors associated with reward and reinforcement, for example feeding behavior, are controlled by distinct components of the endogenous opioid system located in relevant brain regions. It has also been shown that regardless of their i Read More

Opioid receptors (OR) and their mRN A are present in the central and peripheral nervous system of mammals. In this review we examine the behavioral effects of opioids and the expression of their receptors during peripheral inflammation in two experimental models: the rat paw and the mouse intestine. Inflammation increased the antinocice ptive (paw) and the inhibitory effects of opioids in the gut (transit, permeability a Read More

The role of central nervous system (CNS) in regulation of gastric function has long been known. The dorsal vagal complex (DVC) has an important role in regulation of gastric mucosal integrity; it is involved both in mucosal protection and in ulcer formation. Neuropeptides have been identified in DVC, the origin of these peptides are both intrinsic and extrinsic. Neuropeptides are localized also in the periphery, in afferent neurons. Read More

Extensive efforts since 1931, on the structural determination of the mammalian tachykinin SP by NMR, CD and IR have turned out to be inconclusive. Studies are now being concentrated on the structural properties and characteristics of various NK receptors (NK1, NK2 and NK3) with the help of genetics, cloning, receptor engineering, mutagenesis and modeling. This knowledge is now being fruitfully used in the develo Read More

Despite of the recent advances in the structural investigation of complex molecules, the comprehension of the 3D features responsible for the interaction between opioid peptides and μ- opioid receptors still remains an elusive task. This has to be attributed to the intrinsic nature of opioid peptides, which can assume a number of different conformations of similar energy, and to the flexibility of the receptorial cavity, which Read More

In this review the conformational studies of natural enkephalins (H-Tyr-Gly-Gly-Phe- Met-OH the [Met5]enkephalin and H-Tyr-Gly-Gly-Phe-Leu-OH; the [Leu5]enkephalin), their acyclic and cyclic analogues, including those carried out in our laboratory, performed by experimental and theoretical methods and their combination, are described. Emphasis is given on the role of conformational constraints introduced by cyclization on Read More

Determination of conformations and structures of opioid peptides in the membrane environments is an essential step to understand the action of the peptide to the specialized receptors. This information not only gains insight into the structure-function relationship of opioid peptide but also gives proper guidelines to design a new drug to have same neuroendocrine functions. This review provides the structural studies of thre Read More

The availability of new, highly selective antagonists, in the field of opioid peptides and of other pain peptides, is important both for a better understanding of the interaction of the receptors with their ligands and for their practical relevance. The design of antagonists is not obvious even when the essential features of agonists are well known. In this review we have examined the main aspects of the problem using, as lead Read More

Darvas, F.; Keseru, G.; Papp, A.; Dorman, G.; Urge, L.; Krajcsi, P. Curr. Top. Med. Chem. 2002, 2, 1287-1304. In this manuscript, several paragraphs were directly copied from an earlier publication written by a different author without proper attribution (Clark, D. E. Combinatorial Chemistry and High Throughput Screening 2001, 4, 477-496). Specifically, the lead paragraph under “General Concepts in Absorption” on page 1288 an Read More