Understanding how drugs and diseases are associated in the molecular level is of critical importance to unveil disease mechanisms and treatments. Until recently, few studies attempt end to discover important gene modules shared by both drugs and diseases.

Two beta-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities by asymmetric hydrogenation of unprotected amino ketones for the first time by using Rh catalysts bearing electron-donating phosphine ligands. A series of alpha-primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and with good enantioselectivies. This Rh electron-donating phosphine-catalyzed asymmetric hyderogenation represents one of the most promising and convenient approaches towards the asymmetric synthesis of chiral amino alcohols.

Stress echocardiography is valuable, non-invasive method useful for detection of coronary artery disease. In stress echocardiography myocardial ischemia is most commonly induced by exercise or pharmacological agents like dobutamine, dypiridamole, arbutamine or adenosine. The aim of the study was to compare usefulness of dobutamine-atropine stress echocardiography (DATR) with dobutamine-adenosine stress echocardiography (DADE) in detection of coronary artery disease. Studies were carried out in 23 patients, 11 women and 12 men, with suspected coronary artery disease. Both DATR and DADE were performed in all patients. In DATR left ventricular segmental contractility was estimating during intravenous infusion of dobutamine in increasing doses from 5 to 40 microg/kg/min and after intravenous administration of 1 mg of atropine. In DADE regional left ventricular systolic function was analyzed during intravenous infusion of dobutamine in increasing doses from 5 to 40 microg/kg/min and adenosine in dose of 0.14 mg/kg/min. The sensitivity of DATR in detection of coronary artery disease was 87% and specificity was 85%, whereas DADE 87% and 100% respectively. The sensitivity of DATR and DADE in subgroups of patients with one-vessel and multivessel disease was equal: 83% and 90% respectively. There were no significant differences between DADE and DATR in respect of sensitivity and specificity in detection of coronary artery disease. The results of this study suggest that dobutamine-adenosine stress echocardiography is highly sensitive and specific diagnostic test for detection both one-vessel and multivessel coronary artery disease. Moreover, there is no statistically important difference between dobutamine-adenosine stress echocardiography and dobutamine-atropine echocardiography in respect of sensitivity and specificity in detection of coronary artery disease.

A number of pharmaceuticals are employed as diagnostic agents for cardiovascular diseases. Four groups of agents are reviewed here: 1) vasoactive substances employed as adjuncts to physical maneuvers in diagnosis of structural heart disease; 2) vasodilators used to produce heterogeneity of coronary flow; 3) sympathomimetic agents simulating the effects of exercise on the heart for the purpose of detection of coronary artery stenosis; and 4) ultrasonic contrast agents used to enhance myocardial imaging for the assessment of segmental wall motion. In the first group are amyl nitrate, a vasodilator, and methoxamine and phenylephrine, both vasopressors. The vasodilators of the second group are dipyridamole and adenosine. When combined with scintigraphic perfusion imaging or with echocardiographic assessment of segmental wall motion, these agents can detect single- or multiple-vessel coronary artery disease with sensitivity and specificity comparable to submaximal exercise. They are especially useful for preoperative risk assessment before noncardiac surgery. The sympathomimetic agents of the third group, dobutamine and arbutamine, increase myocardial contractility and heart rate, and dilate the peripheral vasculature. As with the vasodilators, when combined with nuclear or echocardiographic techniques they are equivalent to exercise in detection of coronary disease. They are especially useful in patients with bronchospastic disease and for assessment of myocardial viability. Agents from groups 2 and 3 have acceptable side-effect and safety profiles. The last group reviewed includes echocardiographic contrast agents that, in this investigative setting, are employed to enhance detection of segmental wall motion when used with agents from groups 2 and 3.

[reaction: see text] Syntheses of variously modified ligands for the dinuclear zinc catalysts for the asymmetric aldol and nitroaldol (Henry) reactions are reported. Catalytic enantioselective nitroaldol reactions promoted by these modified ligands led to efficient syntheses of the beta-receptor agonists (-)-denopamine and (-)-arbutamine.

Nuclear radiology is valuable in assessing pathophysiology of a variety of organ systems. Pharmacologic interventions are often employed in radionuclide imaging to monitor the physiologic changes, which in turn facilitate the diagnosis. Metoclopramide, erythromycin, and cisapride have been used for gastric emptying studies. To overcome false-negative results, cimetidine, pentagastrin, and glucagon have been used in imaging of Meckel diverticula. Pharmacologic intervention with either cholecystokinin-8 or morphine is used primarily for the assessment of diseases of the gallbladder, common bile duct, and sphincter of Oddi. Pharmacologic interventions performed during renography include diuretic administration, angiotensin-converting enzyme inhibition, and aspirin renography. Recombinant thyrotropin can be used in patients with previously treated thyroid carcinoma who require lifelong follow-up for recurrent disease. Cardiac pharmacologic stress agents fall into two categories: coronary vasodilating agents, such as dipyridamole and adenosine, and cardiac positive inotropic agents, such as dobutamine and arbutamine. Measurement of hemodynamic responses to pharmacologic flow augmentation with carbon dioxide or acetazolamide is valuable in cerebrovascular perfusion studies.

Ischemic heart disease is the leading cause of death in the developed countries for those older than 65 years of age. In patients suspected to have coronary artery disease a stress test should be performed to identify the vulnerability of the myocardium to ischemia. As a rule of thumb, the evaluation of coronary artery disease is best done by exercise stress test. In patients who are not able to exercise adequately, pharmacological stress agents are used. The commonly used agents are the coronary vasodilators, adenosine and dipyridamole and the catecholamines, dobutamine and arbutamine. These agents are combined with imaging techniques to increase the sensitivity and specificity of the test. These agents have been widely used and have an excellent safety profile. Another advantage in using pharmacological stress agents is that they do not affect the image quality, especially with echocardiography and magnetic resonance imaging. Ongoing developments hold promise for safer and more reliable pharmacological stress agents in the future.