Current Pharmaceutical Design - Volume 11, Issue 25, 2005

Drug discovery and development is time consuming and a costly procedure. The challenges for pharmaceutical companies range from the evaluation of potential new drug candidates, the determination of drug pharmacokinetics/pharmacodynamics, the measurement of receptor occupancy as a determinant of drug efficacy, and the pharmacological characterisation of mechanisms of action. Radiolabelled molecul Read More

Over the last two decades, SPECT (single photon emission computed tomography) and especially PET (positron emission tomography) have proven increasingly effective imaging modalities in the study of human psychopharmacology. Abusing populations can be studied at multiple times after abstinence begins, to give information about neurochemical and physiological adaptations of the brain during recovery from addiction. I Read More

Positron Emission Tomography is a high-resolution, sensitive, functional imaging technique, which can efficiently give access to the distribution, pharmacokinetics and -dynamics of a drug in vivo and which can therefore advantageously play a key-role in both drug discovery and development. This molecular imaging technique requires the preparation of a positron-emitting radiolabelled probe or radiotracer and f Read More

Membrane and vesicular monoaminergic transporters, responsible for the homeostasis of neurotransmitter pools at nerve endings, are very involved in the physiology and diseases of central nervous system. Recent progresses of cerebral molecular imaging using SPECT and PET methods allow the extend of in vivo exploration of these transporters. For this aim, an increasing number of radiopharmaceuticals labelled with [1 Read More

Better mechanistic understanding of disease through mapping of the human and mouse genomes enables rethinking of human infirmity. In the case of cancer, e.g., we may begin to associate disease states with their underlying genetic defects rather than with the organ system involved. That will enable more selective, nontoxic therapies in patients who are genetically predisposed to respond to them. Because one of the Read More

Hypertension is one of the most powerful cardiovascular risk factors. By lowering blood pressure, antihypertensive drug treatment reduces the incidence of stroke and coronary heart disease. In general, the currently recommended antihypertensive agents (α-blockers, angiotensin converting-enzyme inhibitors, angiotensin type-1 receptor blockers, β-blockers, calciumchannel blockers, and diuretics) provide similar c Read More

During the last 20 years, the renin-angiotensin system (RAS) has become an increasingly important focus of basic and clinical cardiovascular research. One main conceptual step forward was made with the discovery of a tissue RAS and the understanging of its critical pathophysiological role in atherogenesis and plaque destabilisation [1]. Major effort to find new strategies for blocking the RAS has produced new classes of Read More

Vasopeptidase inhibition is a novel treatment approach in cardiovascular disease such as hypertension and heart failure. Since the inhibition of the angiotensin-converting enzyme (ACE) turned out to represent a very successful principle in the treatment of hypertension in numerous large scale clinical studies, their results encouraged attempts to inhibit other key enzymes in the regulation of vascular tone as well - such as the ne Read More

The evidence that high levels of endogenous ouabain (EO), a closely related isomer of ouabain, are implicated in human hypertension and cardiac hypertrophy and failure stimulated the pharmacological research for developing novel anti-hypertensive agents active as ouabain antagonists. The pathogenetic mechanisms through which increased EO levels affect cardiovascular system involve the modulation of Na-K ATPase, the k Read More

Nitric oxide (NO) is thought to reduce blood pressure by evoking vasodilation either directly by causing relaxation of vascular smooth muscle or indirectly by acting in the rostral brainstem to reduce central sympathetic outflow, which decreases the release of norepinephrine from sympathetic nerve terminals. An increasingly large body of literature suggests that alterations in the NO system may play an important r Read More

Purpose of Review: Since in hypertensive populations, concentration on peripheral blood pressure only does not achieve 100% of blood pressure-attributable risk reduction, taking into consideration other hemodynamic parameters than peripheral blood pressure could perhaps improve cardiovascular prevention. The main purpose of this review is to analyse the scientific data in favour of considering arterial stiffness par Read More