Exp 1 Introduction to Experimental Pharmacology PDF

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Introduction to Experimental Pharmacology...

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Exp. No. 1

Introduction to Experimental Pharmacology Aim: To study history and scope of experimental pharmacology Pharmacology is the science which deals with the study of drugs. The word ‘pharmacology’ is derived from the Greek words pharmakon (a drug or poison) and logos (discourse). It broadly covers the information about the history, source, physiochemical properties, physiological actions, mechanism of action, absorption, distribution, metabolism, excretion and therapeutic uses of drugs. Experimental pharmacology is one of the cornerstones of the drug discovery process. The medicinal chemist may create the candidate compound, but the pharmacologist is the one who tests it for physiologic activity. A promising compound is investigated by many other scientists—toxicologists, microbiologists, clinicians—but only after the pharmacologist has documented a potential therapeutic effect. A Brief History of Experimental Pharmacology Experimental pharmacology is a relatively young science, arising from the great progress in chemistry and physiology of the 19th century. At the beginning of the 19th century, chemistry made it possible to isolate active substances from medicinal plants, starting with morphine in 1806. Physiology provided the methodology for pharmacology to become an independent medical discipline. Knowledge of chemistry and physiology together formed the basis for experimental pharmacology. The French physiologist François Magendie introduced animal experimentation for scientific research and performed one the first pharmacological experiment to study the action of Nux vomica (a strychnine-containing plant) on dogs, and showed that the spinal cord was the site of its convulsant action. In 1849, Rudolf Buchheim founded the first experimental pharmacology laboratory at his house in Germany. Buchheim turned the purely descriptive and empirical study of medicines into an experimental science . He claimed that the effects of a drug could best be studied by isolating the substance, investigating its chemical composition and correlating the chemistry of drug with changes it caused in the function of organs. Oswald Schmiedeberg, Buchheim’s most prominent follower, set up a new laboratory for experimental pharmacology in Strasbourg, then a German city. In 1869, Schmiedeberg showed that muscarine evoked the same effect on the heart as electrical stimulation of the vagus nerve. In 1872, Oswald Schmiedeberg became a professor of pharmacology at the University of Strasbourg, received generous government support in the form of a magnificent institute of pharmacology. Schmiedeberg was recommended for his post by Carl Ludwig, the great physiologist from Leipzig. Preceding his appointment in Strasbourg, Schmiedeberg had been trained in experimental methodology at Ludwig’s Institute in Leipzig. Buchheim, Schmiedeberg and Ludwig adapted the research methods of physiology and brought modern pharmacology into being. In the United States, the first chair in pharmacology was established at the University of Michigan in 1890 under John Jacob Abel, an American who had trained under Schmiedeberg. His major accomplishments include the isolation of

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epinephrine from adrenal gland extracts (1897–1898), isolation of histamine from pituitary extract (1919), and preparation of pure crystalline insulin (1926). His student Reid Hunt discovered acetylcholine in adrenal extracts in 1906.

The two most important methods introduced early in the development of pharmacologic techniques, the use of the kymograph and the method of keeping an isolated organ alive. The kymograph was the first device used to document records of experiments, contributing critically to the emergence of pharmacology as an independent science. Pharmacologists adopted the new kymographic methods of conducting physiological experiments for the recording of drug effects, registering changes in physiological function caused by the administration of drugs as a variable in time. It was found that an isolated organ or tissue remained functional for several hours in a bath containing a physiologic salts solution (PSS) through which oxygen was bubbled. Henrick Magnus (1802 –1870) first applied this method to a strip of the small intestine, Jean-François Heymans (1904) worked with the mammalian heart, and Claude Bernard experimented with isolated nerve-muscle preparations. These were a great improvement for experimental pharmacology techniques. In India, Sir Ram Nath Chopra made the beginning in pharmacological research of traditional drugs. The other outstanding pharmacologists who significantly contributed to the growth of this discipline in India are R. B. Amra, M. N. Ghosh, U. K. Sheth, P. C. Dandiya, S. K. Kulka rni, K. P. Bhargava and many others. Scope of Experimental Pharmacology Today the experimental pharmacology has tremendously drifted from the conventional approach to molecular and biochemical aspects. The advancements in the field of electrophysiology, biochemistry, and molecular biology and electronic or digital recording systems and software have enriched and broadened the horizons of experimental pharmacology. The main tasks of pharmacologists in the search for and development of new medicines are to: (1) Find out a therapeutic agent suitable for human use; (2) Study the toxicity of drugs (3) Study the mechanism and site of action of drugs. For better health care and to provide more effective, safe and affordable medications research is continuously being carried on new chemicals. Since experimental pharmacology involves the discovery of new drugs or to study the actions of existing drugs it is done in two main stages: (i)

Preclinical experimental pharmacology which involves the identification and optimization of novel chemical lead structures and testing them on animals and animal tissues or organs for their biological actions.

(ii) Clinical pharmacology where testing of drugs is done on human volunteers and patients for assessing the pharmacokinetics, safety and efficacy in humans. Animals are not easily available nowadays due to animal welfare regulations and ethics. Animal experiments are expensive, time-consuming and tedious. Thus with the changing scenario, alternative methods of teaching pharmacology experiments have been developed along with the advances in computer technology. Animal

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experiments can be substituted by demonstrations using computer-simulated learning programs. Various softwares are available for computer simulation demonstrations. Exercises in the form of graphs, tables obtained from various animal experiments can be used to teach the students. Exact simulation of real animal experiments on a computer is not easy because the biological responses are very complex. Many factors come to control an organ or a system. Hence, the results obtained with these simulated models may not be very accurate. References 1.

Kulkarni S. K. Hand book of experimental pharmacology. Vallabh Prakashan, Delhi

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Bronswijk and Cohen. The first recordings of pharmacological effects. British Journal of Clinical Pharmacology. 2008; 66(5):588–593

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