Enhancer uptake inhibitory effect

Tramadol has about one tenth the pain-relieving ability of morphine.53 There are two enantiomers, and both contribute to pain relief, but via different mechanisms. (+)-Tramadol and the metabolite (+)-0-desmethy 1-tramadol, which is referred to as Ml, are agonists of the mu opioid receptor. (+)-Tramadol inhibits serotonin reuptake and (-)-tramadol inhibits norepinephrine re uptake.25 This latter action enhances the inhibitory effects on pain transmission in the spinal cord. Because the actions of the two enantiomers are complementary, they are usually supplied as a racemic mixture. However, because it is a serotonin-reuptake blocker, interaction with other medications can lead to the occurrence of serotonin syndrome.54... 

With the development of (-)-l-phenyl-2-propylaminopentane, (-)-PPAP, the (-)-deprenyl analogue free of the MAO-B inhibitory potency, we already furnished direct evidence that the enhanced dopaminergic activity following administration of (-)-deprenyl was unrelated to the inhibition of MAO-B. Because (-)-PPAP, like (-)-deprenyl, inhibited the uptake of tyramine in isolated smooth muscle tests, we first assumed that the drug-induced enhanced dopaminergic activity was due to an uptake inhibitory effect. Further studies revealed that this interpretation was false. 

A total of 16-22 Cu + ions have been shown to bind relatively tightly to the 24-meric horse spleen apoferritin and to have a small catalytic effect on the aerobic oxidative uptake of Fe + [32], This observation is particularly surprising given that Zn + has an inhibitory effect on the oxidative uptake of Fe + by horse spleen apoferritin [33, 34]. As noted above, Zn + inhibits the ferroxidase activity of E. coli bacterioferritin by binding to the binuclear center [20, 21] and thus it was of some interest to investigate the effect that Cu " has on the aerobic oxidative uptake of Fe + by , coli bacterioferritin. As described below, Cu + enhances the catalytic activity of bacterioferritin as far as Fe " " oxidation is concerned. 

The effects on sleep result from the psychostimulant and sympathomimetic actions of these drugs. They enhance noradrenergic, dopaminergic and serotonergic transmission in the central and peripheral nervous system mainly by increasing transmitter release and also inhibitory uptake. 

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