Paradoxical effect

Jacobsen, KA (1998) Adenosine A3 receptors novel ligands and paradoxical effects. Trends Pharmacol. Sci. 19 184-191. 

But there is also a third aspect to our expectancies for improvement, and that is the speed with which the change is expected. I might expect change to occur almost immediately, or I might expect it to happen gradually over time. This is the aspect of our expectations that can have paradoxical effects. When people have unrealistic expectations, when they expect too much change to occur too quickly, their expectations are likely to be shattered. 

The failure of physostigmine to reverse BZ effects during the first 8 hours (Fig. 8) is interesting and unexplained. It reminds one of the Berry and Davies findings (in 1970 at the British labs in Porton Down) which showed that the reversible anticholinesterase pyridostigmine was paradoxically effective as a prophylactic agent in the event of nerve gas exposure (see ref. ). 

As early as the 1940s it became clear that amphetamine could also produce a calming effect in adults prone to aggression and agitation. Later, this so-called paradoxical effect was also seen in children with hyperkinetic syndrome, the precursor to ADHD. 

Nair AR, Boersma LJ, Schilz L, Chaudhry MA, Muschel RJ, Chaudry A. (2001) Paradoxical effects of trichostatin A Inhibition of NE-Y-associated histone acetyltransferase activity, phosphorylation of hGCN5 and down-regulation of cyclin A and B1 mRNA. Cancer Lett 166 55-64. 

McEwen BS, Angulo J, Cameron H, et al Paradoxical effects of adrenal steroids on the brain protection vs. degeneration. Biol Psychiatry 31 177-199, 1992 McCarvey K, Zis AP, Brown EE, et al ECS-induced dopamine release effects of electrode placement, anticonvulsant treatment and stimulus intensity. Biol Psychiatry 34 152-157, 1993... 

Paradoxical effects cognitive impairment and perseverative behavior are occasionally seen in children treated with psychostimulants. According to Greenhill et al. (1999) such phenomena are indicative of a drug overdose and will improve at dose reduction. Constriction of attention or overfocusing as a consequence of treatment with psychostimulants has been another critical issue (Breggin, 1999). Based on an extensive review of the literature and their own experience, Wilens and Biederman (1992) assert that there is no evidence of such phenomena at doses up to 1.0 mg/kg of methylphenidate. 

Anecdotal case reports and small sample size trials have shown some benefit for the use of psychostimulants to manage episodes of excitability in mania. This counterintuitive, paradoxical effect parallels their beneficial use in children with hyperactivity ( 277). The theoretical basis may be related to an indirect effect of these agents that leads to enhancement of 5-HT functioning. 

Soloff PH, George A, Nathan RS, et al. Paradoxical effects of amitriptyline on borderline patients. Am J Psychiatry 1986 143 1603-1605. 

This disrupting effect is probably characteristic of all opioids. In contrast to humans, a number of species (cats, horses, cows, pigs) may manifest excitation rather than sedation when given opioids. These paradoxic effects are at least partially dose-dependent. 

Jacobson KA, Siddiqi SM, Olah ME, Ji XD, Melman N, Bellamkonda K, Meshulmam Y, Stiles GL, Kim HO (1995) Structure-activity relationships of 9-alkyladenine and ribose modified adenosine derivatives at rat A3 adenosine receptors. J Med Chem 38 1720-1735 Jacobson KA (1998) Adenosine A3 receptors novel ligands and paradoxical effects. Trends Pharmacol Sci 19 184-191... 

Boudouris O, Ferrand S, Guillet JL, Madelenat P. Effets paradoxaux du tamoxifene sur l uterus de la femme. [Paradoxical effects of tamoxifen on the woman s uterus. 

There is a class of curvilinear dose-response relationships in toxicological and epidemiological studies that may be described as U-shaped or J-shaped curves. Other terms such as biphasic, and more recently hormesis, have been used to refer to paradoxical effects of low-level toxicants. In brief, these dose-response curves reflect an apparent improvement or reversal in the effect of an otherwise toxic agent. These... 

Increase in TAC is not always a good prognostic it may simply indicate an initial response to oxidative stress, as with concentrations of individual antioxidants and activities of antioxidant enzymes, or when it is due to disturbances in uric acid metabolism. Because uric acid is the main determinant of TAC of blood plasma, TAC increases in situations when the concentration of urate is increased, for example, in metabolic disorders and kidney failure. TAC is increased in urine from renal transplant recipients with delayed graft function (SI6). Ischemia of small intestine leads to an increase in TAC of rat blood serum, which is maximal (almost twofold) immediately after termination of 45-min ischemia (S22). TAC of blood plasma of rats poisoned with a high dose of carbon tetrachloride (1200 mg/kg, intraperitoneal injection, measurement 16 hr after injection) was significantly (over twofold) increased (Kl). These apparently paradoxical effects can be explained, however, by release of antioxidants from cells undergoing necrosis. Increase in TAC after intensive physical exercise also may be a marker of tissue... 

Hodges YK, Reese SM, Rahl PM, Horwitz LD. Paradoxical effects of iron chelation on growth of vascular endothelial cells. J Cardiovasc Pharmacol. 2005 45(6) 539-544. 

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