E. Martinotti

Bio: E. Martinotti is an academic researcher from University of Perugia. The author has contributed to research in topics: Alpha (ethology) & Pirenzepine. The author has an hindex of 10, co-authored 25 publications receiving 276 citations.

Highly potent 1,4-benzothiazine derivatives as K(ATP)-channel openers.

Abstract: A series of 1,4-benzothiazines, suitably functionalized at the N-4 and C-6 positions, arising from the replacement of a benzopyran-based structure of cromakalim with a 1,4-benzothiazine nucleus, has been synthesized as potassium channel openers (KCOs). Most of the tested compounds show high vasorelaxant potency that is considerably higher than that of the reference levcromakalim (LCRK). In the presence of the well-established selective K(ATP) blocker, glibenclamide, the vasorelaxing effects were antagonized in a competitive fashion, indicating the involvement of the K(ATP) channel in their pharmacological effect. Some aspects of the structure-activity relationship associated with the N-4 and C-6 substituents are discussed. The highest level of activity was achieved with a cyclopentenone ring at the N-4 position coupled with an electron-withdrawing group such as nitro, trifluoromethyl, or cyano at the C-6 position. Compounds 4c, 5c, and 6c displayed a vasorelaxant potency at least 10 000 times greater than that of LCRK, thus becoming the most potent KCOs identified to date.

An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives.

Abstract: On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenoceptors; the beta 2/beta 1 selectivity ratio indicated that they are more active on the tracheal than on the cardiac beta-receptor. The chemical reactivity of the AOEDs was studied through the calculation of the electrostatic molecular potential (EMP) on a model compound in its preferred conformation. The results showed that the EMP trend agrees with that previously calculated for other beta-blocking drugs.

Torsadogenic cardiotoxicity of antipsychotic drugs: a structural feature, potentially involved in the interaction with cardiac HERG potassium channels.

Abstract: Many non-cardiovascular drugs of common clinical use cause, as an unwanted accessory property, the prolongation of the cardiac repolarisation process, due to the block of the HERG (Human Ether-a-go-go Related Gene) potassium channel, responsible for the repolarising IKr current. This delayed cardiac repolarisation process can be often unmasked by a prolongation of the QT interval of the ECG. In these conditions, premature action potentials can generate morphologically anomalous after-polarisations, and trigger a dangerous kind of polymorphic ventricular tachyarrhythmia, known as torsade de pointes, which can evolve in ventricular fibrillation and death. The risk associated with the torsadogenic cardiotoxicity of drugs, which prolong the QT interval has been the topic of documents produced by many health authorities, giving important issues about the preclinical and clinical evaluation of cardiac safety. Besides, public and private research laboratories developed several experimental in vitro or in vivo strategies, aimed to an early recognition of the influence of a drug (or of a drugcandidate) on the HERG channel and / or on the cardiac repolarisation process. Also the identification of a possible pharmacophore model, common in all or at least in numerous torsadogenic drugs, could represent a first step for the development of useful in silico approaches, allowing a preliminary indication about the potential torsadogenic property of a given molecule. In this work, we described the electrophysiological basis of torsade de pointes and listed several pharmacological classes of torsadogenic drugs. Among them, we focused our attention on antipsychotics, with an accurate overview on the experimental and clinical reports about their torsadogenic properties. Moreover, a common structural feature exhibited by these drugs, despite of their remarkable chemical differences, is evidenced by a computational approach and is indicated as a possible “facilitating” requirement for their torsadogenic properties. Together with other remarks, coming from different computational studies, the individuation of a satisfactory “toxicophore” model could be greatly useful, for the theoretical prediction of torsadogenic properties of a given chemical moiety and for the design of new drugs devoid of such an undesired and potentially lethal side-effect.

Vasoconstrictor activity of 8-O-acetylharpagide from Ajuga reptans.

Abstract: The traditional therapeutic indications for the use of Ajuga reptans (Labiatae) have been investigated. The H2O-soluble part of a crude and partially purified MeOH extract and two isolated iridoids (8-O-acetylharpagide and harpagide), were tested for a biological activity on isolated smooth muscle preparations from guinea pig.

Effects of subacute exposure to noise on the noradrenergic innervation of the cardiovascular system in young and aged rats: a morphofunctional study.

Abstract: The effects of subacute noise stress on the noradrenergic pattern and receptor-mediated responses were examined in aorta and atria of young and aged rats. Noise exposure increased the density of noradrenergic fibres and responses to the β-adrenergic agonist isoprenaline in the cardiac tissue of young animals. In aged rats, the stressing stimulus markedly increased the maximal response to the α-agonist on the aortic musculature; on the contrary, a reduced responsiveness to the β-agonist was observed at the cardiac level, without any noteworthy changes in the noradrenergic pattern in comparison to aged controls. The present results indicate that subacute noise stress induces both morphological and functional modifications of the noradrenergic nervous system and also that after subacute noise stress, morphological changes do not necessarily correspond exactly to functional data; the latter show responses that are more widely differentiated than the morphological ones.

Bioisosterism: A Rational Approach in Drug Design.

Abstract: Years of cumulative research can result in the development of a clinically useful drug, providing either a cure for a particular disease or symptomatic relief from a physiological disorder. A lead compound with a desired pharmacological activity may have associated with it undesirable side effects, characteristics that limit its bioavailability, or structural features which adversely influence its metabolism and excretion from the body. Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. The concept of bioisosterism is often considered to be qualitative and intuitive.1 The prevalence of the use of bioisosteric replacements in drug design need not be emphasized. This topic has been reviewed in previous years.2-5 The objective of this review is to provide an overview of bioisosteres that incorporates sufficient detail to enable the reader to understand the concepts being delineated. While a few popular examples of the successful use of bioisosteres have been included, the George Patani graduated with a B.Pharm. in 1992 from the College of Pharmaceutical Sciences, Mangalore University at Manipal, India. In 1996, he received his M.S. in Pharmaceutical Science at Rutgers University under the direction of Professor Edmond J. LaVoie. He is presently pursuing graduate studies in pharmaceutics. His current research interests are focused on drug design and controlled drug delivery.

How and why environmental noise impacts animals: an integrative, mechanistic review.

Abstract: Ecology Letters (2011) 14: 1052–1061 Abstract The scope and magnitude of anthropogenic noise pollution are often much greater than those of natural noise and are predicted to have an array of deleterious effects on wildlife. Recent work on this topic has focused mainly on behavioural responses of animals exposed to noise. Here, by outlining the effects of acoustic stimuli on animal physiology, development, neural function and genetic effects, we advocate the use of a more mechanistic approach in anthropogenic environments. Specifically, we summarise evidence and hypotheses from research on laboratory, domestic and free-living animals exposed to biotic and abiotic stimuli, studied both observationally and experimentally. We hope that this molecular- and cellular-focused literature, which examines the effects of noise on the neuroendocrine system, reproduction and development, metabolism, cardiovascular health, cognition and sleep, audition, the immune system, and DNA integrity and gene expression, will help researchers better understand results of previous work, as well as identify new avenues of future research in anthropogenic environments. Furthermore, given the interconnectedness of these physiological, cellular and genetic processes, and their effects on behaviour and fitness, we suggest that much can be learned from a more integrative framework of how and why animals are affected by environmental noise.

Labiatae Family in folk Medicine in Iran: from Ethnobotany to Pharmacology

Abstract: Labiatae family is well represented in Iran by 46 genera and 410 species and subspecies. Many members of this family are used in traditional and folk medicine. Also they are used as culinary and ornamental plants. There are no distinct references on the ethnobotany and ethnopharmacology of the family in Iran and most of the publications and documents related to the uses of these species are both in Persian and not comprehensive. In this article we reviewed all the available publication on this family. Also documentation from unpublished resources and ethnobotanical surveys has been included. Based on our literature search, out of the total number of the Labiatae family in Iran, 18% of the species are used for medicinal purposes. Leaves are the most used plant parts. Medicinal applications are classified into 13 main categories. A number of pharmacological and experimental studies have been reviewed, which confirm some of the traditional applications and also show the headline for future works on this family.