Search and Development of New Bronchodilators with Prolonged Action
Tech Area / Field
- MED-DRG/Drug Discovery/Medicine
- CHE-SYN/Basic and Synthetic Chemistry/Chemistry
- CHE-THE/Physical and Theoretical Chemistry/Chemistry
3 Approved without Funding
State Research Institute of Organic Chemistry and Technology, Russia, Moscow
- Russian State Medical University, Russia, Moscow
- Southern Illinois University / School of Medicine / Department of Pharmacology, USA, IL, Springfield
Project summaryThe objective of this Project is to design the powerful and competing bronchodilator of new generation for the treatment of bronchial diseases. Its action is based on blocking of peripheral muscarinic M1 and M3 acetylcholine receptor systems.
A difference of the proposed bronchodilator from widespread pharmaceuticals is in:
– its prolonged action that makes possible to use it not only for efficient treatments, but as a potential prophylactic mean;
– the capability to stimulate the biosynthesis of receptor protein de novo as it has been demonstrated by preliminary experiments.
The design and development of new highly efficient pharmaceuticals to be used for treatments of bronchial diseases outline currently burning problem in the world over. Nowadays, bronchial diseases increasingly rise in the number and become one of the mostly spread health risk factors. Furthermore, there is a threatening tendency of growing the cases of bronchial diseases. This is why, leading pulmonologists are pinning their hopes on current searches for new specific potential drugs and application of inhalatory and peroral medicaments with prolonged action.
A methodology of searching and design of long-term and powerful bronchodilators is based on concepts on the mechanism of complex formation between drug molecules and acetylcholine receptors. It is possibly to vary the lifetime of drug-receptor complexes from few hours to several days, depending on the chemical structure of ligand molecules. The foregoing are fundamentals of scientific and technical approaches to solving the Project tasks.
Highly qualified specialists in various fields of science will work cooperatively on the problem of searching for the optimal structure of new bronchodilators.
During the Project implementation, some methods must be developed for synthesis of labeled and unlabeled bronchodilators. Quantochemical calculations of basic and optimal chemical structures will be done for computer design of new potential drugs. The action mechanism of biologically active compounds will be studied in details.
Pharmacological and toxicological properties of new compounds and potential bronchodilating substance will be assessed by standard methods in compliance to requirements of Pharmacological Committee of Russian Federation.
It is expected to determine the pharmacokinetic and pharmacodynamic parameters of potential bronchodilating drugs, which are to be optimal for the humans, from in vivo tests on various animal species with the use of new mathematical models developed by authors of Project. In view of the above methods, a new procedure for animal-to-human interspecies scaling of active doses is of particular significance.
Implementation of Project will result in the design of the new generation bronchodilator, which will be different from the existing analogs by that its medication and pretreatment is due to prolonged specific binding to peripheral M1- and М3-subtype muscarinic acetylcholine receptors, but not to multiple injections.
Project objectives and expected results are fully in compliance to ISTC goals proclaimed to redirect the activity of former weapon scientists and specialists for solving peaceful tasks. High qualification and unique experience of the personnel, availability of necessary tech- and labware, and advanced level of researches will warrant the successful implementation of these Project.