Weird results in this study on Oxolinic acid

[aced126]

Here is a study of the stimulant properties of Oxolinic acid: http://www.europeanneuropsychopharmacology.com/article/S0924-977X(97)00083-7/abstract

Just from the abstract itself there are some things which don't seem right. D2 receptor antagonism results in insignificant reversal of stimulant effects but D1 blockade inhibits the effect, whereas haloperidol would block the stimulant effects of amphetamine.

Furthermore, this structure does not reverse reserpine-induced akinesia (whereas amphetamine does) and when in fact inhibits amphetamine reversal of akinesia. IC50 for DA uptake is 4.3 micromolar.

Any explanation for these results?

 

[anubis23]

"D1 receptors stimulate the enzyme adenylyl cyclase, which is responsible for synthesizing cAMP. Consequently, the rate of cAMP formation is increased by stimulation of D1 receptors. In contrast, D2 receptor activation inhibits adenylyl cyclase, thereby decreasing the rate of cAMP synthesis. These opposing effects can occur because the receptors activate two different G proteins, Gs in the case of D1 receptors and Gi in the case of D2 receptors...In some cells, D2 receptor stimulation activates a G protein that subsequently enhances K+ channel opening...leading to hyperpolarization"

- Psychopharmacology Drugs the Brain and Behavior by Meyer, Quenzer.
Haloperidol is also not limited and targets quite a lot of receptors. Additionally it is an inverse agonist.

As for the second point keep in mind amphetamine is a competitive inhibitor of DAT however I forget if this is true of dexamphetamine. Also amphetamine is a releasing agent and is not limited to dopamine, and has additional effects at TAAR.

Here are some useful toxicity studies. http://www.ema.europa.eu/docs/en_GB...sidue_Limits_-_Report/2009/11/WC500015338.pdf