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The current study examined the ability of antimalarials chloroquine (CQ), primaquine (PQ), and quinine (Q) to inhibit human erythrocyte membrane acetylcholinesterase (AChE) and the mechanisms underlying their inhibitory action. CQ was found to be the most effective inhibitor of the enzyme followed by PQ and Q. The concentrations required to obtain 33% inhibition (IC 33 ) for CQ and PQ were 22 and 38 µM, respectively, whereas that for Q was 3.2 mM. The concentrations required to obtain 67% inhibition (IC 67 ) were about 9 and 7 times higher for CQ and PQ, whereas that for Q was only about 2.5 times higher. Hill plot analysis revealed that CQ shows de-binding above 40 µM. The two kinetic components of AChE were inhibited by the three antimalarials, and the inhibition was of mixed type. Increasing concentrations of antimalarials caused progressive decrease in the V max of both components. IC 33 concentrations resulted in 1.6- to 6-fold increase in K m of both the components while IC 67 concentration caused 2.8- to 13-fold increases in K m with maximum effect being seen with Q. The K i values were lowest for CQ suggesting that it was the most potent inhibitor; these values were 3.3 and 60 times higher for PQ and Q. Antimalarials represent the bifunctional compounds that possess anti-inflammatory properties and also inhibit cholinesterases. The results of our studies suggest that 4-aminoquinoline–based antimalarials like CQ and hydroxychloroquine, which are both potent anti-inflammatory agents and inhibitors of cholinesterases, may have potential use as the most effective neuroprotective agents against amyloid-β-peptide (Aβ) neurotoxicity in Alzheimers disease. [ABSTRACT FROM AUTHOR]

Effects of in vivo treatment with the three antimalarials chloroquine, primaquine and quinine on rat liver mitochondrial energy transduction functions were examined. Treatment with all the three antimalarials decreased the state 3 and state 4 respiration rates drastically. The extent of inhibition was higher with pyruvate + malate as the substrate than with glutamate. The antimalarials also acted as uncouplers. The uncoupling effect was seen on site II and site III of phosphorylation; site I was unaffected. As a consequence the ADP phosphorylation rates also decreased significantly. Following antimalarials treatment the basal and Mg2 +stimulated ATPase activities increased while the DNP-stimulated ATPase activity was reduced by half. Treatment with chloroquine resulted in decreased contents of cytochromes aa3 and b; primaquine and quinine treatments increased the contents of the two cytochromes in 14 day treatment groups. [ABSTRACT FROM AUTHOR]

Dexamethasone— a potent synthetic glucocorticoid— has multiple therapeutic applications and, used in all age groups, as well as for antenatal and perinatal treatments. However, side-effects of dexamethasone treatment, including those on development, are becoming increasingly apparent. Since developmental processes are energy-dependent, we examined the effects of chronic dexamethasone treatment on oxidative energy metabolism in liver mitochondria from rats belonging to different developmental age groups. Dexamethasone treatment adversely affected the state 3 respiration rates in 2- and 3-week groups and in the adults with glutamate as the substrates, whereas for pyruvate + malate, the adverse effects were seen for the 3 week rats and the adult groups. Oxidation of succinate was severely impaired in all the age groups rats. For ascorbate + TMPD as the substrate, elevated respiration was noted for the 5-week group and the impaired oxidation was observed in adults. Dexamethasone treatment also resulted in site-specific uncoupling with the effect being seen predominantly in the 3- and 5-week and adult animals. The activity of dehydrogenases decreased in a manner comparable to the respiration rates. The mitochondrial cytochromes decreased in an age-dependent manner. The ATPase activity also decreased significantly. The results thus emphasize the adverse effects of dexamethasone treatment on mitochondrial energy metabolism especially in critical age groups. [ABSTRACT FROM AUTHOR]