Novel medicines

For the past few years, however, there has been a hiatus in the pace of discovery of novel medicinal agents. It has been postulated by some that the field has now slowed down due to the limitations of the almost strictly empirical approach that has been applied to date to drug development. It is possible, too, that the higher standards of efficacy and safety that a new drug must meet today, combined with the enormously increased costs of clinical trials, have acted to keep all but the most promising new drugs off the market. 

Is the drug a novel medicine in an otherwise poorly treated and severe disease ... 

Many early claims of having prepared simple 1-hydroxyindoles have proved to be unfounded, although the unusually stable l-hydroxy-2-phenylindole was obtained in 1895.1-Hydroxyindole itself polymerizes on attempted isolation, while O-acylation, O-alkylation, or the presence of substituents greatly stabilizes the molecule. One 1-hydroxyindole antibiotic has been identified and is the only 1-hydroxyindole derivative isolated from natural sources so far. In contrast, a substantial number of 1-methoxyindoles occurs in various plants, and some of these may inhibit tumor formation in mammals. The biochemistry of these compounds, which include 1-methoxy-indoles, -indolines and -2-oxindoles, has not been widely investigated and could be a very fruitful area for new research which might well lead to novel medicinal agents and other useful compounds. 

In collaboration with various medical institutions of Ukraine and Russia, the Institute of Surface Chemistry of the NAS of Ukraine has developed a novel medicinal preparation Silics (the term silics is derived from silica and the institute of Chemistry of Surface), and designed a nanotechnology for its production.2,3 This bioactive silica (BAS) is distinguished for its extended surface and high adsorption properties. 

In several papers the Kunos group has reported observations that may represent a starting point for novel medicinal chemistry research in this area [167, 168], Anandamide (i.v. bolus 4 mg/kg) caused a triphasic blood pressure response, brief hypotension, followed by a transient pressor and then a prolonged depressor phase. The hypotensive effect was not initiated in the CNS, but was due to a presynaptic action that inhibited norepinephrine release from sympathetic nerve terminals in the periphery (heart and vasculature). The inhibitory effect (but not the pressor effect) was antagonized by SR141716A, indicating that this peripheral action was mediated by CB receptors. 

The chances of discovering a truly novel medicine, i.e. one that does something valuable that had previously not been possible (or that does safely what could only previously have been achieved with substantial risk), are increased when the development programme is founded on precise knowledge, at molecular level, of the biological processes it is desired to change. The commercial rewards of a successful product are potentially enormous and provide a massive incenhve to developers to invest and risk huge sums of money. 

The responsibility to protect public health on the one hand yet to allow timely access to novel medicines on the other, is one shared by drug regulators and developers. It is complicated by an ever increasing awareness of the risks and benefits (real, or perceived) of medicines by the general public. 

In the Centralised Procedure a Rapporteur and a Co-Rapporteur, appointed from within the member states of EU, have to evaluate the product and report to the European Medicines Agency within 210 days. If the UK is selected as Rapporteur or Co-Rapporteur, the evaluation of the medicinal product is carried out by the MHRA. Occasionally, when there is particular interest in a novel medicinal product, or when a new medicinal product would have a significant affect on drug usage in the NHS, the MHRA will get involved and opinions will be sought from scientific advisory committees. A recent example of this was when the first inhaled formulation of human insulin was licensed. 

Why is the biopharmaceutical community making such monumental efforts to discover novel delivery technologies Alternate delivery systems may have highly desirable attributes and improved utilities40 for the clinical administration of novel medicinal and chemotherapeutic agents. These attributed included the following ... 

The endocannabinoid system contributes to the control of hypothalamic regulatory mechanisms. We do not know (yet) in which part of the hypothalamus the endocannabinoids are synthesized, but it is possible that cannabinoid receptors, present in the hypothalamus, are activated by AEA or other endocannabinoids released/synthesized quite far away. There is also the possibility that endocannabinoids act on presynaptic membranes to modulate die release of various neurotransmitters. Also of interest is the hypothesis that endocannabinoids may participate in hormone-cytokine networks that regulate reproduction, as this opens new perspectives for the development of novel medicines for human infertility. Acknowledgements. 

The impact of novel medicines for unmet medical needs brought forward by the pharmaceutical industry in the last thirty years is tremendous drugs for metabolic diseases (cholesterol, hypertension, diabetes), HIV treatments, new antibiotics, treatments for rheumatoid arthritis, schizophrenia, etc. These medicines have profoundly transformed the treatment paradigm in their respective fields, with a major impact of extending and enhancing human life. 

Diversity and focussed approaches aie likely to continue to provide complementaiy benefits. The portfolio of techniques will together provide a still more effective and comprehensive approach to the effective identification of novel medicines for the multitude of novel targets that ate being revealed through genomics and proteomics. 

In the past few deeades there has been a hiatus in the momentum of research and discovery of novel medicinal compounds . This particular trend in drug development perhaps is augmented due to two vital factors, namely first, strict empirical and rational approach to drug design and secondly, high standards of safety and therapeutic efficacy together with tremendous increased costs of research and development and finally the clinical trials. 

There really aren t any problems that are more complicated, or more satisfying from a human perspective, than producing novel medicines. ... 

UL medicines are medicines under an rmlicensed dosage form obtained after manipulation of the original dosage form (e.g. crush-ing/cutting tablets, extemporaneous preparations, special ). Sometimes the drug itself may have no licence at all (e.g. chemicals used in metabolic diseases, such as betaine to treat homocystinuria, and novel medicines). Imported medicines become rmlicensed in the country into which they are imported. 

---