Drug development and hormesis: Changing conceptual understanding of the dose response creates new challenges and opportunities for more effective drugs

Current Opinion in Drug Discovery and Development

Volumn 9, Issue 1, 2006, Pages 117-123

  Calabrese, Edward J ^a   Staudenmayer, John W ^a   Stanek, Edward J ^a  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

Author keywords

Biphasic; Drug development hormesis; U shaped

Indexed keywords

ANTINEOPLASTIC AGENT;

ALZHEIMER DISEASE; CELL PROLIFERATION; COGNITION; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFICACY; HORMESIS; HUMAN; HUMAN CELL; MODEL; NONHUMAN; QUANTITATIVE ANALYSIS; REVIEW; TUMOR CELL;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; CHOLINESTERASE INHIBITORS; COGNITION; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; HUMANS; INHIBITORY CONCENTRATION 50; MICROBIAL SENSITIVITY TESTS; NO-OBSERVED-ADVERSE-EFFECT LEVEL; YEASTS;

EID: 30744475471     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (28)

1. Shackell LF, Williamson W, Deitchman MM, Datzman GM, Kleinman BS: The relation of dosage to effect. J Pharm Exp Therap (1924) 23:53-65.
2. Shackell LF: The relation of dosage to effect II. J Pharm Exp Therap (1925) 25:275-288.
3. Calabrese EJ, Baldwin LA: The frequency of U-shaped dose-responses in the toxicological literature. Toxicol Sci (2001) 62(2):330-338.
4. Calabrese EJ, Baldwin LA. The hormetic dose response model is more common than the threshold model In toxicology. Toxicol Sci (2003) 71(2):246-250.
5. Calabrese EJ, Baldwin LA: Toxicology rethinks its central belief. Nature (2003) 421(6924):691-692.
6. Calabrese EJ, Blain R: The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: An overview. Toxicol Appl Pharmacol (2005) 202(3):289-301.
7. Calabrese EJ: Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences. Environ Poll (2005) 138(3):379-412. Provides a comprehensive general review of the hormetic concept.
8. Calabrese EJ, Baldwin LA (Guest editors): Scientific foundations of hormesis. Crit Rev Toxicol (2001) 31:351-695.
9. Calabrese EJ: Alzheimer's disease drugs: An application of the hormetic dose response model. Crit Rev Toxicol (2006): manuscript in preparation.
10. Calabrese EJ: Cancer biology and hormesis: Human tumor cell lines commonly display hormetic (biphasic) dose responses. Crit Rev Toxicol (2005) 35(6):463-582. Provides a comprehensive documentation of hormetic dose responses observed in human tumor cell lines.
11. Calabrese EJ: Hormetic dose-response relationships in Immunology: Occurrence, quantitative features of the dose-response, mechanistic foundations and clinical implications. Crit Rev Toxicol (2005) 35(2-3):89-295.
12. Calabrese EJ: Special Issue: Hormesis: Environmental and biomedical perspectives - Introduction. Crit Rev Toxicol (2003) 33(3-4):213-214.
13. Holbeck SL: Update on NCI in vitro drug screen utilities. Eur J Cancer (2004) 40(6):785-793.
14. Calabrese EJ, Staudenmayer J, Stanek EJ: Hormesis is more common than the threshold model in NCI anti-tumor screening data. (2005): manuscript in preparation.
15. Faessel HM, Levasseur LM, Slocum HK, Greco WR: Parabolic growth patterns in 96-well plate cell growth experiments. In Vitro Cell Dev Biol Animal (1999) 35(5):270-278.
16. Piegorsch W, Bailer AJ: Statistics for Environmental Biology and Toxicology: Interdisciplinary Statistics. Chapman and Hall, New York, NY, USA (1997).
17. Seber GAF, Wild CJ: Nonlinear Regression. John Wiley & Sons, New York, NY, USA (1989).
18. Cox C: Threshold dose-response models in toxicology. Biometrics (1987) 43(3):511-523.
19. Callahan BG, Gaylor D, Stanek EJ 3rd: Introduction: Quantitative and statistical procedures to detect and estimate hormetic effects. Human Ecological Risk Assess (2001) 7(4):779-780.
20. An M: Mathematical modeling of dose-response relationship (hormesis) in allelopathy and its application. Nonlinearity Biol Toxicol Med (2005) 3(2):153-172.
21. Brian P, Cousens R: An equation to describe responses where there is stimulation of growth at low doses. Weed Res (1989) 29:93-96.
22. Schabenberger O, Tharp BE, Kells JJ, Penner D: Statistical tests for hormesis and effective dosages in herbicide dose response. Agronomy J (1999) 91:713-721.
23. Stratton LO, Petrinovich L: Post-trial injections of an anticholinesterase drug and maze learning in two strains of rats. Psychopharmacologia (Berl) (1963) 26:47-54.
24. Carlton PL: Brain acetylcholine and habituation. Prog Brain Res (1968) 28:48-60.
25. Warburton DM, Brown K: The facilitation of discrimination performance by physostigmine sulphate. Psychopharmacologia (1972) 27(3):275-284.
26. Giacobini E: The second generation of cholinesterase inhibitors: Pharmacological aspects. In: Cholinergic Basis for Alzheimer Therapy: Advances in Alzheimer Therapy. Becker R, Giacobini E (Eds), Birkhauser, Boston, MA, USA (1991):247-296.
27. Flood JF, Landry DW, Jarvik ME: Cholinergic receptor interactions and their effects on long-term memory processing. Brain Res (1981) 215(1-2):177-185.
28. Flood JF, Smith GE, Cherkin A: Memory retention: Potentiation of cholinergic drug combinations in mice. Neurbiol Aging (1983) 4(1):37-43.