New disciplines and directions in drug development

EPP News Bureau - Chennai

IPC 2003

‘‘Nuclear Medicine Imaging will be a major focus in drug development efforts in the next decade as we enter a new age of certainty, where diseases will be viewed as molecular dissonance or communication disorder,’’ said Rakesh Kumar Sharma, joint director, Institute of Nuclear Medicine and Allied Sciences (INMAS), Delhi, while highlighting the emergence of radiopharmaceuticals as an important discipline and the development of scanners with higher sensitivity to monitor the functional effects of a drug.

According to him nuclear medicine (NM) can leverage the advancements in molecular biology, pathology and design of next generation drugs. Addressing the audience of the 55th Indian Pharmaceutical Congress at Chennai, Sharma pointed how NM have been successful in the process of evaluating pharmaceutical dosage forms.

‘‘Nuclear medicine can speed up the drug development process, especially when a drug is tested in animals with the use of dedicated high resolution animal scanners, which assess the time course of uptake of a drug in experimental animals,’’ he said. ‘‘NM techniques are used to provide dynamic, non-invasive and real time information on the in vivo behaviours of radiolabeled molecules, he said while explaining radiopharmaceuticals as ‘‘compounds linked to radionuclides that are tailored for preferential localisation in a particular organ or physiologic/pathologic process,’’ he added.

He explained that pharmaceuticals labelled with single-photon emitting radionuclides are exploited to provide high-resolution images on Planar Gama Camera or Single-Photon Emission Computed Tomography (SPECT) scanner. Thus, NM can accurately calculate the time course of uptake, the spatial distribution and the functional effects of a drug.

He observed that the introduction of cyclotron-produced short-lived positron-emitting isotopes of the basic elements of life such as carbon, nitrogen & oxygen, etc, and Positron Emission Tomography (PET) have added interesting dimensions to the applications such as the assessment of blood flow and metabolism, receptor imaging, elucidating the pathophysiologic process, evaluating role of labelled therapeutic agents.

Sharma highlighted the potential of these techniques in the development of novel therapies and in the monitoring of their therapeutic responses. ‘‘Using relevant radiopharmaceuticals, it is possible to characterise cell membrane and macromolecular receptor recognition sites such as receptors, enzymes and neurotransmitters,’’ he said and added, ‘‘Also, we can understand the molecular interactions of biological processes in living systems.’’

Knowledge of the anatomical distribution and localisation of radiolabeled drugs inside the living systems could be used to generate real time receptor occupancy and off-rate studies. Sharma explained the major role played by the functional imaging methodologies in understanding the basic mechanisms of a multitude of disorders, accurate diagnosis of certain diseases, multidrug resistance phenomenon and developing effective treatment for serious illnesses such as cancer and central nervous system maladies.

‘‘As the radiolabeled drug are administered in subpharmacological doses, preliminary studies on their pharmacokinetics and the assessment of their effects on metabolism can be safely carried out even before the drug has entered in phase I trails. Such studies can provide cost-effective predictive toxicology data and information on the metabolism and mode of action of drugs.’’

Participating in a plenary session of the congress, S P Gupta, Professor of Chemistry, Birla Institute of Technology and Science (BITS), Pilani said that rationalisation of drug discovery could drastically reduce the cost and time of investigating a potential drug against any disease.

He emphasised that rationalisation should address certain crucial areas like the identification of the features or physicochemical properties of a molecule affecting the drug’s activity and the ways to predict the activity of any drug molecule before its synthesis.

According to him, the quantitative structure-activity relationship (QSAR) and molecular modelling studies hold great promise in the future. Shiv Kumar Agarwal, vice-president, Orchid Chemicals and Pharmaceuticals, who was one of the speakers of the congress highlighted the significant research directions in the development and marketing of novel antibacterial agents.

‘‘Since the discovery of penicillin, pharmaceutical industries have produced number of synthetic or semisynthetic antibacterial agents to combat a wide variety of bacterial infections. The major classes of antibacterial agents, apart from penicillins, are cephalosporins, monobactams, carbapenems, sulfonamides, tetracyclins, aminolglycosides, quinolones, macrolides and glycopeptides,’’ he said.