title: For the love of paradox: from neurobiology to pharmacology.
abstract: The acute and chronic effects of certain drugs can often be opposite. For example, in congestive heart failure acute administration of β-adrenoceptor agonists results in beneficial improvement in symptoms of the disease, but their chronic use increases mortality. Conversely, certain β-adrenoceptor antagonists/inverse agonists (β-blockers) initially cause a detrimental response by decreasing cardiac contractility in congestive heart failure, whereas chronic treatment with the same β-blockers improves contractility and survival. Furthermore, this time-dependent reversal of outcomes occurs in nonpharmacological interventions, such as exercise, and can even be observed in the response of plants to pruning or other stressors, with the results being a different short-term versus long-term effect. Here, we review some of these phenomena with a special emphasis on the temporal dissociation of pharmacological effects. Although Francis Colpaert used this knowledge to lead a drug discovery project for an analgesic compound that initially produced hyperalgesia, we focused on examples outside the central nervous system.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas 77204-5037, USA. RABond@UH.Edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bond
authors.forename: Heather
authors.initials: H
authors.lastname: Giles
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D054314:Drug Inverse Agonism; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D010146:Pain / Q000188:drug therapy; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000700:Analgesics