Clinical Research - Past, Present & Future

Om D Gulati


Clinical pharmacology/research has a very interesting history. It started in the 40’s of the 20th century through the pioneering work of Harry Gold at Cornell University New York. Clinical research is an integral part of drug development. Drug development can be hastened by a number of new techniques with reduction in cost. In addition reverse pharmacology approaches for drug discovery have come to occupy a special place. 85% of the neutral antagonists act as inverse agonists. Inverse agonists have a distinct effect on receptor regulation as opposed to neutral antagonists.

Orphan receptors constitute about 50% of the GPCRs. It is estimated that now there are nearly 175 orphan receptors after 125 having been deorphanised. Targeting these orphan receptors can lead to about the same number of ligands and antagonists thereof. Polymorphism of cytochrome P450 provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. It is estimated that such personalized P450 gene-based treatment would be relevant for 10-20% of all drug therapy.

Key Words:  Clinical Pharmacology (a facet of clinical research) - Human experiments for safety and efficacy; G-protein coupled receptors (GPCRs) – some orphan receptors ;

Strategies for drug discovery – Deorphanisation of orphan receptors, allosteric receptor sites, in-silico drug screening

Full Text:



Patil PN, Gulati OD, Balaraman R, Goyal RK (2005). Topics in the History of Pharmacology: 133, BS Shah Prakashan, Ahmedabad.

Edzard E (2010). Homeopathy : “A helpful placebo” or an unethical intervention? Trends Pharmacol Sci 31:1.

Edzard E (2010). Invited response to letter by Paula Ross for Tips. Trends Pharmacol Sci 31: 297-298.

Rang HP, Dale MM, Ritter JM, Moor PK (2005). Pharmacology: Churchill & Livingston (An imprint of Elsevier).

Gold H, Cattell M, Otto HL, Kwit NT, Kramer ML (1942). A method for the bio-assay of digitalis in humans. J Pharmacol & Exper Therap 75: 196-206.

Paton WDM – Animal experiment and medical research: a study in evolution (Forty-seventh Stephen Paget Memorial Lecture, 23 October 1978). Reprinted from ’Conquest’ February 1979 (169), 1-14.

Lawrence DR, Bennet PN (1992). Clinical Pharmacology: Churchill & Livingston.

Begaud B (2000). Dictionary of Pharmacoepidemiology: John Wiley & Sons.

Stephen AD, Eliot H, Douglas CJ (2004). Techniques : Cardiovascular Pharmacological Drug Discovery in the 21st century. Trends Pharmacol Sci 25: 225-233.

Ehrlich P. Chemotherapeutische trypanosomen-studien. In: Himmelweit F, editor. The collected papers of Paul Ehrlich. London: Pergamon Press; 1956-1960. 3: 81-103.

Langley JN (1905). On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curare. J Physiol 33: 379-399.

Clark AJ. (1933). Model of action of drugs on cells: Williams and Wilkins Company, Baltimore.

Laurence LB, John SL, Keith LP, Goodman & Gilman’s (2005). The Pharmacological Basis of Therapeutics: 1 – 39, McGraw Hill (Medical Publishing Division, New Delhi).

Katzung BG (2004): Basic and Clinical Pharmacology: 24-25. Mcgraw Hill Education Asia.

Martin VA, Winter C, Brecht S, et al. (2001). The sequence of human genome. Science 291: 1304-1351.

Bare DJ, Lauder J, Wilkie MB, Maness PF, Baldwin (2001). Initial sequencing and analysis of the human genome. Nature 409 : 860-921.

Cacace A, Banks M, Spicer T, Civoli F, Watson J (2003). An ultra HTS process for the identification of small molecule modulators of orphan G-protein coupled receptors. Drug Discov Today 8 : 785-792.

Jeffry MS, Selagh W, Berk JB (1997). Orphan G-protein coupled receptors; neglected opportunity for pioneer drug discovery. Trends Pharmacol Sci 18 : 430-437.

Sidath K, Anthony D (2003). Emerging roles of G-protein coupled receptors in cardiovascular system. Trends Pharmacol Sci 24 : 30-35.

Katie L, Patrick MS, Arthur CC (2007). Allosteric GPCR modulators; taking advantage of permissive receptor pharmacology. Trends Pharmacol Sci 28 : 382-389.

Magnus I – Sundburg (2004). Pharmacogenetics of P450 and its applications in drug therapy; the past, present and future. Trends Pharmacol Sci 25 : 193-200.

Idico A, Peter E (2006). Computational neuropharmacology; dynamic approaches in drug discovery. Trends Pharmacol Sci 27: 240-243.


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.