Presence Of Quinine Research Articles

ChemInform Abstract: Catalytic Asymmetric Synthesis of Highly Functionalized Compounds with Six Contiguous Stereocentres.

AbstractTreatment of the epoxy anhydride (I) or the N‐phenylaziridino analogue (V) with the alcohols (II) in the presence of quinine as the chiral base results in cleavage of the heterocyclic rings, forming the optically active hydroxy lactones (III) and (IV) or the phenylamino lactones (VI) and (VII).

Synthesis of Optically Active β-Ketosulphides Catalysed by Quinine/Quinidine and Homogeneous Catalysts

Abstract Thiophenol (I) reacts with Mannich bases (IV) in the presence of quinine, quinidine, and homogeneous catalysts derived from these bases giving rise to optically active ketosulphides (V). Absolute configuration of the product (IV B) was determined by converting the product to known 3-phenyl-butane-2-one.

The effects of quinine on the calcium and magnesium content of the sarcoplasmic reticulum and the temperature-dependence of quinine contractures

A significant decrease in the Ca2+ and increase in the Mg2+ content of the terminal cisternae (TC) of the sarcoplasmic reticulum (SR) during quinine contraction was demonstrated by electron probe analysis of rapidly frozen frog muscles. The extent of Ca2+ release (71% of total) from the TC and the absence of an increase in total cell Ca2+ support the conclusion that quinine contractures are caused by passive efflux of Ca2+ from the SR when the latter is uncompensated due to inhibition of the SR Ca2+ pump by quinine. A rapid warming contraction (RWC) was observed, in the presence of quinine, when the temperature of intact and skinned muscles was increased from about 5 degrees C to 18-23 degrees C. The duration of the latency of quinine contracture, in intact muscle bundles, was approximately 31 s at 3 degrees C and 2 s at 23 degrees C. The results suggest a significant temperature sensitivity of the passive Ca2+ channels of the SR membrane, although an effect of temperature on the lipid partition coefficient of quinine into the SR has not been ruled out.

Rapid enzyme-linked immunosorbent assay (ELISA) with a visual end-point for detecting quinine in urine, serum and dried blood spots.

A rapid and simple assay has been developed for the detection of quinine in biological fluids (e.g., urine, serum and dried blood spots). The assay has a coloured end-point and a limit of sensitivity of 3 µg l–1, using 5-µl samples. No cross-reactivity is observed with examples of commonly administered drugs. The assay was used to screen samples of dried blood spots and urine from a volunteer after taking a dose of 300 mg of quinine. The assay requires no sophisticated laboratory equipment or instrumentation to give a qualitative assessment of the presence of quinine, but may be used with a simple portable microtitre plate reader to give quantitative measurements if required.

ChemInform Abstract: Optical Induction. Part 7. Reaction Between Phenyloxirane and Benzylamine.

AbstractReaction of the oxirane (I) with benzylamine (II) in the presence of quinine (A1) or quinidine (A2) results in the formation of the alcohol (III).

Chemically reinforced conditioned courtship in Drosophila: responses of wild-type and the dunce, amnesiac and don giovanni mutants.

To test the hypothesis that associative learning is the basis for conditioned courtship, male Drosophila melanogaster were paired with virgin females in the presence of quinine, known to be a negative reinforcer in a learning paradigm independent of courtship. Such "experienced" wild-type males failed to court virgin females and remained refractory to them for 1-2 h. But experienced males from the learning-defective strain, dunce, continued to court females at high levels; and experienced males from the retention-defective strain, amnesiac, failed to demonstrate the wild-type refractory period. Finally, males from the don giovanni strain, defective with respect to fertilized-female conditioning, were conditioned by presentation of virgin females and quinine. Courtship-depressing effects of cis-vaccenyl alcohol, which can be recovered from fertilized females, were confirmed, but no evidence for its role as a negative reinforcer of male courtship was obtained.

Effect of quinine on plasma digoxin concentration and renal digoxin clearance.

In order to explore the digoxin-quinine interaction, digoxin steady state pharmacokinetics was studied before and during quinine coadministration in seven healthy subjects. Quinine (250 mg/day) increased mean plasma digoxin concentration from 0.64 +/- 0.12 to 0.80 +/- 0.18 ng/ml (p less than 0.05) within one week. Urinary digoxin recovery rose from 154.0 +/- 18.8 to 181.5 +/- 22.6 micrograms/24 h (p less than 0.01), whereas renal digoxin clearance was unaltered in the presence of quinine (181.5 +/- 24.2 vs. 174.1 +/- 26.5 ml/min). An increase in quinine dose (to 750 mg/day) caused further increments in plasma digoxin levels, whereas renal digoxin clearance remained unchanged. Quinine elevates plasma digoxin concentrations in a stepwise fashion probably due to an impairment of extrarenal digoxin clearance.

The control of 86Rb efflux from rat isolated pancreatic islets by the sulphonylureas tolbutamide and glibenclamide.

The efflux of 86Rb from rat isolated pancreatic islets preloaded with the isotope and perifused in vitro, has been used to monitor the effects of sulphonylureas on the potassium permeability, Pk, of pancreatic beta-cells. Tolbutamide (5 microM to 5 mM) had a dual effect, causing initially a decrease in 86Rb efflux (the 'on' response) which was rapidly superseded on drug removal by a large phasic increase in 86Rb efflux (the 'off' response). Each kinetic response had a different dose-dependency: the 'on' response was half-maximal at tolbutamide concentrations of 0.02 mM, maximal at 0.2 mM and decreased by concentrations greater than 0.2 mM whereas the 'off' response was half-maximal at 0.07 mM, maximal at 0.7 mM, with further increases in concentration (up to 5 mM) causing no further change in magnitude. Analysis of the time- and concentration-dependency of tolbutamide action, by presenting increasing concentrations (0 to 1.4 mM) of tolbutamide as a ramp or step function, established a critical dependence of the kinetics of 86Rb efflux during and after exposure to tolbutamide upon the initial rate of increase of the tolbutamide concentration rather than its final steady state. In the presence of quinine (10 microM), D600 (50 microM), or tetraethylammonium (20 mM), the secondary increase in 86Rb following tolbutamide (0.7 mM) removal was totally inhibited. Co2+ (2.56 mM) not only blocked the secondary 'off' response but also potentiated the initial 'on' response of tolbutamide. Glibenclamide produced a rapid decrease in 86Rb efflux but at a much lower concentration (10 microM) than tolbutamide and with no 'off' response apparent over a wide range of concentration (1 to 100 microM); moreover the decrease in 86Rb efflux was sustained and only slowly reversible. It is concluded that tolbutamide has two opposing actions on islet beta-cell 86Rb efflux, and therefore PK: (i) a tendency to increase a calcium-sensitive PK by stimulating calcium entry into the cell and (ii) a decrease in PK that may be due to a direct effect on the calcium-sensitive PK itself. The more sustained pharmacological action of glibenclamide is explained by the longer-lasting decrease in PK that it produces.

A new method for the endpoint determination in argentometry using halide-sensitive fluorescent indicators and fiber optical light guides

Titration of halide solutions with silver(I) nitrate in the presence of quinine or acridine in acidic solution results in a maximum in fluorescence intensity at the equivalent point. This effect is due to dynamic fluorescence quenching of the indicators by halide and silver(I) ion, respectively. Since fluorescence can easily be measured with the help of bifurcated fiber optical light guides, the method offers a simple means for following titrations of halides.

Na+--K+ pump activity and the glucose-stimulated Ca2+-sensitive K+ permeability in the pancreatic B-cell.

A rise in the extracellular concentration of glucose from an intermediate to a high value changes the burst pattern of electrical activity of the pancreatic B-cell into a continuous firing, and yet activates the B-cell Ca2+-sensitive K+ permeability. The hypothesis that glucose exerts such effects by inhibiting the Na+, K+-ATPase was investigated. Ouabain (1 mM) mimicked the effect of 16.7 mM glucose in stimulating 86Rb, 45Ca outflow and insulin release from perifused rat pancreatic islets first exposed to 8.3 mM glucose. The stimulation by ouabain of 86Rb outflow was reduced in the absence of extracellular Ca2+ and almost completely abolished in the presence of quinine, and inhibitor of the Ca2+-sensitive K+ permeability. In the presence of ouabain, a rise in the glucose concentration from 8.3 to 16.7 mM failed to stimulate 86Rb outflow. However, the rise in the glucose concentration failed to inhibit 86Rb influx in islet cells, while ouabain dramatically reduced 86Rb influx whether in the presence of 8.3 or 16.7 mM glucose. These findings do not suggest that inhibition of the B-cell Na+, K+-ATPase represents the mechanism by which glucose in high concentration stimulates 86Rb outflow and induces continuous electrical activity in the B-cell.

Regulation of 86Rb + outflow from pancreatic islets I. Reciprocal changes in the response to glucose, tetraethylammonium and quinine

Glucose (16.7 mM), tetraethylammonium (TEA; 10.0 mM) and quinine (0.1 mM) all decreased 86Rb fractional outflow rate from isolated pancreatic islets. At the concentration here used, the effect of glucose was not augmented by TEA, suggesting that glucose affected the TEA-sensitive modality of Rb extrusion. The effects of TEA and quinine were not additive. In the presence of quinine which was as potent as glucose in decreasing 86Rb efflux, an early inhibition of 86Rb outflow was still observed in response to glucose administration. However, the latter inhibition was followed by a glucose-induced secondary rise in 86Rb fractional outflow rate. It is proposed that quinine unmasks a dual or discontinuous effect of glucose upon 86Rb + handling by the islet cells.

Inhibition of Mixed-Lymphocyte Reaction by Quinine and Lack of Effect on Plaque-Forming Cells and Lymphoid-Derived Tumor Cells

Using Balb/c cells as responder cells and mitomycin-treated C57B1 cells as stimulator cells, it was found that quinine was inhibitory in a one-way mixed-lymphocyte reaction. Incorporation of [3H]-TdR was brought down to base levels in the presence of quinine. Quinine was not toxic for antibody-forming cells, and had no effect on plaque-forming cells formed by antibody-committed cells. The degree of [3H]-TdR incorporation of MOPC-315 tumor cells and Burkitt's lymphoma cells was not affected by the presence of quinine in the medium. The cytotoxicity of quinine for mitogen-stimulated cells was demonstrated in soft-agar cultures.

Quinine Inhibition of Host Cell Penetration by Toxoplasma gondii, Besnoitia jellisoni, and Sarcocystis sp. In vitro

The penetration of Toxoplasma gondii, Sarcocystis sp., and Besnoitia jellisoni into cultured cells was significantly inhibited by 0.1 mg quinine sulfate/ml in the inoculation medium. The former 2 organisms were inhibited from penetration by as little as 0.01 mg of this drug. Incubation of either organisms or cells in medium containing quinine prior to inoculation of organisms in quinine-free medium did not significantly reduce penetration. Organisms remained motile in the presence of quinine and the few that entered cells remained intracellular. Results of this study parallel those with Eimeria and indicate that quinine interferes with a mechanism of host cell penetration common to all 4 genera. In vitro methods have been used to study penetration of cells by eimerian sporozoites (Fayer et al., 1970; Roberts et al., 1971; Fayer, 1971). In the latter study, addition of quinine compounds to the inoculation medium inhibited penetration of cultured cells by Eimeria meleagrimitis and E. tenella sporozoites without producing visible cytopathological effects or rendering the organisms immotile. The present study was conducted to determine the effect of quinine sulfate on the penetration of cells by Toxoplasma gondii, Besnoitia jellisoni, and Sarcocystis sp. MATERIALS AND METHODS

Quinine: Effect on Tetrahymena pyriformis—III : Energetics of isolated mitochondria in the presence of quinine and other antimalarial drugs

The effect of quinine, primaquine, quinacrine and chloroquine on substrate oxidation and oxidative phosphorylation was studied in isolated Tetrahymena pyriformis mitochondria. Primaquine and chloroquine stimulated the oxidation of succinate and inhibited oxidative phosphorylation, which indicates that these antimalarials act as uncoupling agents. This activity apparently requires both the quinoline nucleus and the diamino alkane side-chain since neither quinine, which contains only the quinoline nucleus, nor quinacrine, which contains only the side-chain, had a significant effect on oxidative phosphorylation or the oxidation of succinate. Primaquine, chloroquine and quinine inhibited the oxidation of fumarate, malate, β-hydroxybutyrate and glutamate, but had little effect when isocitrate, citrate, or α-ketoglutarate were used as substrates. Since primaquine and chloroquine stimulate electron transfer with succinate, these results indicate an inhibition of the enzyme systems which oxidize these substrates. Otherwise, an increased respiratory rate would have been observed upon addition of primaquine or chloroquine. The pattern of inhibition was similar for all three antimalarials and may be because of the quinoline moiety common to these drugs. Quinacrine had no significant effect on any of these reactions.

Quinine and quinidine inhibition of pentobarbital metabolism

The influence of quinine hydrochloride pretreatment on pentobarbital metabolism was assessed by measurements of sleeping times, ld 50 values, hepatic microsomal metabolism and relative rates of decay of plasma levels of pentobarbital. These studies were conducted in Swiss-Webster mice, Sprague-Dawley rats and Angora or Toggenburg goats. Quinine increased sleeping time in phenobarbitalstimulated and unstimulated mice and in rats, decreased the ld 50 of pentobarbital in mice, and increased the plasma half-life of pentobarbital in goats. Quinine in various concentrations inhibited the hepatic metabolism of pentobarbital in 9000 g supernatant incubation mixtures ( K I = 2.9 × 10 −5 M), as did quinidine ( K I = 7.6 × 10 −6 M). Duration of barbital hypnosis was not affected by quinine pretreatment. The presence of quinine in plasma decreased the extent of protein binding of pentobarbital m plasma from humans, ponies, swine, goats and mice. The pentobarbital concentration in brains from quinine-pretreated mice was not significantly different from the concentration in brains from control animals at awakening. The results obtained from these experiments indicate that quinine and quinidine alter the duration of action of pentobarbital by inhibition of microsomal enzymes.

Thrombocytopenic purpura caused by hypersensitivity to quinine.

Abstract Studies are reported on a patient who developed thrombocytopenic purpura on two separate occasions after ingestion of Bromoseltzer and Bromoquinine, the latter containing quinine hydrobromide. After recovery from the second acute episode, test doses with acetanilid, a constituent of Bromoseltzer, failed to produce a significant platelet reduction, whereas 5 mg. of quinine hydrobromide caused a systemic reaction, a marked reduction in platelets, and prolongation of bleeding time. Marked thrombocytopenic purpura with a prolonged bleeding time and petechiae was produced in a normal volunteer after concomitant oral ingestion of quinine hydrobromide and intravenous injection of plasma from the quinine-sensitive patient. No change in platelet counts was observed in the same volunteer when quinine or plasma from the patient was given alone. Platelet agglutinin tests done on plasma from the recipient were negative. In vitro platelet agglutinin tests were consistently positive only when quinine hydrobromide was added to the patient's serum. The serum factor remained active after 199 days' storage at −10 °C. In the presence of quinine, a high panagglutinin titer could still be demonstrated in the patient's blood drawn 203 days after recovery from the second acute episode of thrombocytopenic purpura. No conclusive platelet agglutinins were demonstrable when sodium bromide, acetanilid, or Bromoseltzer were added to the patient's serum. Passive transfer tests using patient's serum and quinine were negative. It is suggested: (a) that the immune mechanism responsible for the thrombocytopenia causes both a peripheral destruction of platelets and transient damage to megakaryocytes, and (b) that the antigen to which antibody is produced is a complex composed of a union between the drug and platelets.

The estimation of strychnine in the presence of quinine

The estimation of strychnine in the presence of quinine

63. Presence of Quinine in the Urine of persons who had taken it in large doses

63. Presence of Quinine in the Urine of persons who had taken it in large doses