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Ra R CH3 R1 N(CH3)2 60 R Ph R' cyclohexyl pirenzepine H2-antagonist therapy for DU continues to be debated, but recent studies suggest a significant improvement over monotherapy (142,143). Antiulcer activity of teienzepine, over and above that due to inhibition of acid secretion, has been demonstrated in rats (144). In a related series of compounds, KW5805 (57) was identified as a potent antiulcer agent in a stress-induced ulcer model in rats, comparable to pirenzepine, but with apparently much...

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12 r, oh, r2 ch2ch2CH2NH2 14 r, h, r2 ch2ch2nhch2ch20h It Is perhaps a greater challenge to design a new antitumor agent from first principles rather than modifying the structure of a known compound with activity The realization that a number of DNA intercalating agents with antitumor activity contain a planar electron-rich ring system tethered to a basic side-chain led to the design of a series of compounds in which a methylaminopropanediol was appended to diverse polycyclic hydrocarbons (38)....

Identification And Evaluation Of New Targets

The technique of gene disruption (or gene transplacement) which was developed for non-pathogenic yeasts and filamentous fungi (47-51) is being extended to pathogenic fungi. Specific gene sequences are isolated and manipulated ex vivo, and then returned to the organism, replacing the normal allele by the modified allele (50-53). When successful, this method establishes whether the isolated gene sequence is essential for the life of the organism, and whether it is associated with virulence. Using...

Cardiovascular And Pulmonary Agents

Robertson, Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana Edward W. Petrillo, Jr., Nick C. Trippodo, and Jack M. DeForrest, The Squibb Institute for Medical Research, Princeton, New Jersey 51 7. Pulmonary and Antiallergy Agents Andrew Shaw, ICI Americas, Inc., Wilmington, Delaware 61 8. Treatment of Acute Myocardial Ischemia Melvin J. Yu and Paul J. Simpson, Lilly Research Laboratories, Eli Lilly & Co., Indianapolis, Indiana 71 John E....

Other Endogenous Vasoactive Peptides

Over the last decade many studies have demonstrated a relationship between endogenous opioid peptides and the cardiovascular system under both homeostatic and pathophysiological conditions (140,141). Further research is clearly required to define the role and mechanism by which endogenous opioids may modify cardiovascular effects. Of the peptides identified to date in cardiovascular nerves the most widely distributed are neuropeptide Y, calcitonin gene-related peptide (CGRP), the tachykinins...

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Droxidopa is a synthetic amino acid precursor of (-)-norepinephrine which is absorbed from the gut and metabolized to norepinephrine. In Parkinsonian patients, droxidopa added to existing levodopa decarboxylase inhibitor therapy produces significant improvements in retropulsion, dysarthria and muscular rigidity refractory to other treatments however, tremor was unaffected. Foscarnet Sodium (antiviral) (33-35) First Introduction Sweden, Netherlands Introduced by Astra Trade Name Foscavir CAS...

Catalytic Antibodies Future Challenges

Are relatively rigid structures, capable of binding with high affinity to antigens, while enzymes are inherently flexible molecules that permit the facile access of substrates to the active site, and the efficient dissociation of products. Scientists will need to learn how to manipulate antibody structure to impart greater flexibility and higher catalytic efficiency. Many of the tools needed to accomplish this are in hand, including site-directed mutagenesis and selective chemical modification,...

Counterregulatory Hormones

Hypoglycemia or stress can trigger the secretion of several hormones, including glucagon, the catecholamines such as epinephrine, growth hormone and Cortisol. These act to counter insulin's action in stimulating peripheral glucose disposal and inhibiting hepatic glucose output (89,90). Modulation of these counterregulatory hormones can impact glycemic control and or insulin action in diabetic patients. Glucagon Receptor Antagonists - Insulin and glucagon maintain euglycemia by balancing glucose...

Chemically And Enzymatically Modified Lipoproteins

Uptake by Macrophages - Cultured mouse peritoneal macrophages MPM take up native LDL to a very small degree and do not accumulate cholesterol esters when exposed to even high concentrations for a long period. Yet LDL modified chemically by acetylation enters the cells by receptor mediated endocytosis this results in a massive cholesterol accumulation within the macrophages 3 . The e-amino group of the lysine residues of apolipoprotein B apo B become blocked by acetylation, the net negative...